Oseltamivir phosphate supplier

Name
Oseltamivir phosphate
EINECS
CAS No. 204255-11-8
Article Data47
CAS DataBase
Density 1.08g/cm3
Solubility
Melting Point 196-198°C
Formula C₁₆H₂₈N₂O₄^.H₃PO₄
Boiling Point 473.3 °C at 760 mmHg
Molecular Weight 410.404
Flash Point 240 °C
Transport Information
Appearance white cyrstalline solid
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms Oseltamivir Phosphate [USAN];ethyl (3R,4R,5S)-4-acetamido-5-amino-3-pentan-3-yloxy-cyclohexene-1-carboxylate; phosphoric acid;GS4104;Ro-64-0796;Ethyl (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (1:1);Tamiflu (TN);GS4071;Tamiflu (*Phosphate salt 1:1*);1-Cyclohexene-1-carboxylic acid, 4-(acetylamino)-5-amino-3-(1-ethylpropoxy)-, ethyl ester, (3R,4R,5S)-, phosphate (1:1);Oseltamivir phosphate (JAN/USAN);
PSA 178.22000
LogP 1.44800

Synthetic route

: 196618-13-0
oseltamivir

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
With phosphoric acid In ethanol at 50℃; for 0.0166667h; Sonication;	98%
With phosphoric acid In ethanol at -18.8℃; for 17h;	89.9%
With phosphoric acid In ethanol at 50 - 55℃;	88.6%

: ethyl (3R,4R,5S)-4-N-acetylamino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Stage #1: ethyl (3R,4R,5S)-4-N-acetylamino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate With palladium 10% on activated carbon; 2,2'-iminobis[ethanol] In ethanol at 68 - 78℃; for 8h; Stage #2: With phosphoric acid In ethanol at 45 - 55℃; Reagent/catalyst;	96.31%
With 1,3-dimethylbarbituric acid; phosphoric acid; palladium 10% on activated carbon; triphenylphosphine In ethanol at 55 - 78℃; Temperature; Reagent/catalyst; Large scale;	89%
Stage #1: ethyl (3R,4R,5S)-4-N-acetylamino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate With tetrakis(triphenylphosphine) palladium(0); 1,3-dimethylbarbituric acid In dichloromethane at 35℃; for 7h; Inert atmosphere; Stage #2: With phosphoric acid In ethanol at 48 - 52℃; for 2h;	85%

: 204255-06-1
oseltamivir

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Stage #1: oseltamivir With tributylphosphine; triphenylphosphine In ethanol; water at 50℃; for 3h; Stage #2: With phosphoric acid In ethanol	92%
Stage #1: oseltamivir With Lindlar's catalyst; hydrogen In ethanol at 20℃; under 760.051 Torr; for 16h; Stage #2: With phosphoric acid In ethanol; ethyl acetate at 50℃; for 0.5h;	91%
	91%

: 86119-84-8, 7664-38-2
phosphoric acid

: 196618-13-0
oseltamivir

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
In ethanol; water at 50 - 55℃; for 1.5 - 2h;	88%

: 367252-68-4
(3R,4R,5S)-ethyl 4-acetamido-5-((tert-butoxycarbonyl)amino)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
With phosphoric acid In ethanol at 78℃; for 12h; Inert atmosphere;	83%
With phosphoric acid In ethanol at 0 - 78℃; for 15h; Inert atmosphere;	83%
With phosphoric acid In ethanol at 50℃; for 6h;	81%

: (3R,4R,5S)-4-acetamido-5-allyloxycarbonylamino-1-ethoxycarbonyl-3-(3-pentyloxy)cyclohex-1-ene

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Stage #1: (3S,4S,5S)-4-acetamido-5-allyloxycarbonylamino-1-ethoxycarbonyl-3-(3-pentyloxy)cyclohex-2-ene With 1,3-dimethylbarbituric acid; 5%-palladium/activated carbon; triphenylphosphine In ethanol at 80℃; for 1h; Stage #2: With phosphoric acid In ethanol at 50℃;	76%

: 891831-22-4
tert-butyl [(1S,5R,6R)-6-acetylamino-3-cyano-5-(1-ethylpropoxy)cyclohex-3-en-1-yl]carbamate

: 64-17-5
ethanol

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Stage #1: tert-butyl [(1S,5R,6R)-6-acetylamino-3-cyano-5-(1-ethylpropoxy)cyclohex-3-en-1-yl]carbamate; ethanol With hydrogenchloride at 60℃; for 4h; Stage #2: With phosphoric acid at 4 - 50℃;	50%
Stage #1: tert-butyl [(1S,5R,6R)-6-acetylamino-3-cyano-5-(1-ethylpropoxy)cyclohex-3-en-1-yl]carbamate; ethanol With hydrogenchloride Stage #2: With sodium hydroxide Stage #3: With phosphoric acid

: (2-oxo-2,3,3aβ,4α,5,7aβ-hexahydro-benzoxazol-4-yl)-carbamic acid tert-butyl ester

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: LiOH 1.2: NEt3 2.1: isobutyric anhydride; DMSO 3.1: Ni(cod)2; 1,5-cyclooctadiene 3.2: NBS; NEt3 4.1: LiAl(Ot-Bu)3H 5.1: DEAD; PPh3 5.2: 56 percent / BF3*OEt2 6.1: HCl 6.2: aq. NaOH 6.3: H3PO4 View Scheme

: 930275-48-2
(1S,2R)-2-(acetylamino)-1-(tert-butoxycarbonylamino)-4-cyclohexen-3-one

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: Ni(cod)2; 1,5-cyclooctadiene 1.2: NBS; NEt3 2.1: LiAl(Ot-Bu)3H 3.1: DEAD; PPh3 3.2: 56 percent / BF3*OEt2 4.1: HCl 4.2: aq. NaOH 4.3: H3PO4 View Scheme

: (6-acetylamino-5-hydroxy-cyclohex-3-enyl)-carbamic acid tert-butyl ester

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: isobutyric anhydride; DMSO 2.1: Ni(cod)2; 1,5-cyclooctadiene 2.2: NBS; NEt3 3.1: LiAl(Ot-Bu)3H 4.1: DEAD; PPh3 4.2: 56 percent / BF3*OEt2 5.1: HCl 5.2: aq. NaOH 5.3: H3PO4 View Scheme

: 927395-71-9
tert-butyl [(1S,5R,6R)-6-acetylamino-3-cyano-5-hydroxycyclohex-3-en-1-yl]carbamate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: DEAD; PPh3 1.2: 56 percent / BF3*OEt2 2.1: HCl 2.2: aq. NaOH 2.3: H3PO4 View Scheme

: 930275-47-1
(6-acetylamino-3-cyano-5-oxo-cyclohex-3-enyl)-carbamic acid tert-butyl ester

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: LiAl(Ot-Bu)3H 2.1: DEAD; PPh3 2.2: 56 percent / BF3*OEt2 3.1: HCl 3.2: aq. NaOH 3.3: H3PO4 View Scheme

: 204255-04-9
ethyl (3R,4R,5S)-4-amino-5-azido-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.98 kg / sodium bicarbonate / hexane / 1 h 2: 1.) hydrogen, 2.) phophoric acid / 1.) Raney nickel / 1.) ethanol, 16 h, 2.) ethanol, 55 65 deg C View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / water; dichloromethane / 1 h / 20 °C 2: hydrogen / ethanol / 18 h / 760.05 Torr 3: phosphoric acid / acetone; ethanol / Reflux View Scheme
Multi-step reaction with 3 steps 1: pyridine / 1 h / 20 °C 2: hydrogen / ethanol / 10 h 3: phosphoric acid / ethanol / 3 h / 60 °C View Scheme

: 204254-96-6
(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) sodium azide, ammonium chloride, 2.) trimethylphosphine / 1.) ethanol, water, 70-75 deg C, 18 h, 2.) acetonitrile, <38 deg C, 2 h 2: sodium azide, ammonium chloride / dimethylformamide / 18 h / 70 - 80 °C 3: 0.98 kg / sodium bicarbonate / hexane / 1 h 4: 1.) hydrogen, 2.) phophoric acid / 1.) Raney nickel / 1.) ethanol, 16 h, 2.) ethanol, 55 65 deg C View Scheme
Multi-step reaction with 6 steps 1.1: boron trifluoride diethyl etherate / 1.17 h / 0 °C 1.2: 4 h / 0 - 20 °C 1.3: 36 h / 20 °C 2.1: triethylamine; dmap / 1 h / 0 °C 3.1: sodium hydride / dichloromethane; dimethyl sulfoxide; mineral oil / 8 h / 20 °C 4.1: boron trifluoride diethyl etherate / dichloromethane / 0.37 h / -15 °C 5.1: caesium carbonate / dimethyl sulfoxide / 0.25 h / 80 °C 5.2: 0.33 h / 80 °C 6.1: phosphoric acid / ethyl acetate; ethanol / 2 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1.1: sodium azide; ammonium chloride / water; ethanol / 8 h / 70 - 75 °C 1.2: 6 h / Reflux 2.1: sodium azide; ammonium chloride / N,N-dimethyl-formamide / 5 h / 8 - 85 °C 3.1: sodium hydrogencarbonate / water; dichloromethane / 1 h / 20 °C 4.1: hydrogen / ethanol / 18 h / 760.05 Torr 5.1: phosphoric acid / acetone; ethanol / Reflux View Scheme

: 204255-02-7
ethyl-(1R,5R,6R)-5-(pentan-3-yloxy)-7-azabicyclo[4.1.0]hept-3-ene-3-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium azide, ammonium chloride / dimethylformamide / 18 h / 70 - 80 °C 2: 0.98 kg / sodium bicarbonate / hexane / 1 h 3: 1.) hydrogen, 2.) phophoric acid / 1.) Raney nickel / 1.) ethanol, 16 h, 2.) ethanol, 55 65 deg C View Scheme
Multi-step reaction with 4 steps 1: sodium azide; ammonium chloride / N,N-dimethyl-formamide / 5 h / 8 - 85 °C 2: sodium hydrogencarbonate / water; dichloromethane / 1 h / 20 °C 3: hydrogen / ethanol / 18 h / 760.05 Torr 4: phosphoric acid / acetone; ethanol / Reflux View Scheme

: 204254-84-2
ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: 95 percent / perchloric acid 2: 1.) BH3-SMe2, trimethylsilyl trifluoromethanesulfonate, 2.) potassium hydroden carbonate / 1.) dichloromethane, -20 - -10 deg C, 0.2 h, 2.) ethanol, water, 55-65 deg C, 1 h 3: 1.) sodium azide, ammonium chloride, 2.) trimethylphosphine / 1.) ethanol, water, 70-75 deg C, 18 h, 2.) acetonitrile, <38 deg C, 2 h 4: sodium azide, ammonium chloride / dimethylformamide / 18 h / 70 - 80 °C 5: 0.98 kg / sodium bicarbonate / hexane / 1 h 6: 1.) hydrogen, 2.) phophoric acid / 1.) Raney nickel / 1.) ethanol, 16 h, 2.) ethanol, 55 65 deg C View Scheme
Multi-step reaction with 7 steps 1.1: perchloric acid / 18 h 2.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C 2.2: 12 h / 20 °C 2.3: 2 h / 55 - 65 °C 3.1: sodium azide; ammonium chloride / water; ethanol / 8 h / 70 - 75 °C 3.2: 6 h / Reflux 4.1: sodium azide; ammonium chloride / N,N-dimethyl-formamide / 5 h / 8 - 85 °C 5.1: sodium hydrogencarbonate / water; dichloromethane / 1 h / 20 °C 6.1: hydrogen / ethanol / 18 h / 760.05 Torr 7.1: phosphoric acid / acetone; ethanol / Reflux View Scheme

Yield

Multi-step reaction with 6 steps
1: 95 percent / perchloric acid
2: 1.) BH3-SMe2, trimethylsilyl trifluoromethanesulfonate, 2.) potassium hydroden carbonate / 1.) dichloromethane, -20 - -10 deg C, 0.2 h, 2.) ethanol, water, 55-65 deg C, 1 h
3: 1.) sodium azide, ammonium chloride, 2.) trimethylphosphine / 1.) ethanol, water, 70-75 deg C, 18 h, 2.) acetonitrile, <38 deg C, 2 h
4: sodium azide, ammonium chloride / dimethylformamide / 18 h / 70 - 80 °C
5: 0.98 kg / sodium bicarbonate / hexane / 1 h
6: 1.) hydrogen, 2.) phophoric acid / 1.) Raney nickel / 1.) ethanol, 16 h, 2.) ethanol, 55 65 deg C
View Scheme

Multi-step reaction with 7 steps
1.1: perchloric acid / 18 h
2.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C
2.2: 12 h / 20 °C
2.3: 2 h / 55 - 65 °C
3.1: sodium azide; ammonium chloride / water; ethanol / 8 h / 70 - 75 °C
3.2: 6 h / Reflux
4.1: sodium azide; ammonium chloride / N,N-dimethyl-formamide / 5 h / 8 - 85 °C
5.1: sodium hydrogencarbonate / water; dichloromethane / 1 h / 20 °C
6.1: hydrogen / ethanol / 18 h / 760.05 Torr
7.1: phosphoric acid / acetone; ethanol / Reflux
View Scheme

: 204254-90-0
ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.) BH3-SMe2, trimethylsilyl trifluoromethanesulfonate, 2.) potassium hydroden carbonate / 1.) dichloromethane, -20 - -10 deg C, 0.2 h, 2.) ethanol, water, 55-65 deg C, 1 h 2: 1.) sodium azide, ammonium chloride, 2.) trimethylphosphine / 1.) ethanol, water, 70-75 deg C, 18 h, 2.) acetonitrile, <38 deg C, 2 h 3: sodium azide, ammonium chloride / dimethylformamide / 18 h / 70 - 80 °C 4: 0.98 kg / sodium bicarbonate / hexane / 1 h 5: 1.) hydrogen, 2.) phophoric acid / 1.) Raney nickel / 1.) ethanol, 16 h, 2.) ethanol, 55 65 deg C View Scheme
Multi-step reaction with 6 steps 1.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C 1.2: 12 h / 20 °C 1.3: 2 h / 55 - 65 °C 2.1: sodium azide; ammonium chloride / water; ethanol / 8 h / 70 - 75 °C 2.2: 6 h / Reflux 3.1: sodium azide; ammonium chloride / N,N-dimethyl-formamide / 5 h / 8 - 85 °C 4.1: sodium hydrogencarbonate / water; dichloromethane / 1 h / 20 °C 5.1: hydrogen / ethanol / 18 h / 760.05 Torr 6.1: phosphoric acid / acetone; ethanol / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: caesium carbonate / N,N-dimethyl-formamide / 8 h / 90 - 100 °C 2.1: triethylsilane; titanium tetrachloride / dichloromethane / 2 h / -40 - -35 °C / Inert atmosphere 3.1: acetic acid; sulfuric acid / 1 h / 0 - 20 °C 4.1: 1,3-dimethylbarbituric acid; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 7 h / 35 °C / Inert atmosphere 4.2: 2 h / 48 - 52 °C View Scheme

: 367252-67-3
(3R,4R,5S)-4-azido-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethyl ester

: 86119-84-8, 7664-38-2
phosphoric acid

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
With sodium hydroxide; hydrogen bromide; acetic anhydride; acetic acid; triethylamine; cobalt In ethanol; ethyl acetate; acetone

: ethyl (3R,4R,5S)-4-(acetylamino)-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate tartrate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
With phosphoric acid In ethanol; acetone at 25 - 30℃; for 1.5h;

: 891862-23-0
(1S,5S,6R)-ethyl 7-acetyl-5-(tert-butoxycarbonylamino)-7-azabicyclo[4.1.0]hept-2-ene-3-carboxylate

: 584-02-1
2-pentanol

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 2.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2.2: 4 °C View Scheme

: 119719-61-8
(1R,4R,5R)-4-iodo-6-oxabicyclo[3.2.1]octane-7-one

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 13 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 6 h / Reflux 2.1: potassium carbonate / 5 h / 20 °C 3.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 6.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 6.2: 1 h 7.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 8.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 8.2: 0.5 h / -78 °C / Inert atmosphere 8.3: 0.5 h 9.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 10.1: triphenylphosphine / toluene / 3 h / Reflux 11.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 12.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 13.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 13.2: 4 °C View Scheme
Multi-step reaction with 12 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 6 h / Reflux 2.1: potassium carbonate / 5 h / 20 °C 3.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 6.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 6.2: 1 h 7.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 8.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 8.2: 0.5 h / -78 °C / Inert atmosphere 8.3: 0.5 h 9.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 9.2: 3 h / Reflux 10.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 11.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 12.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 12.2: 4 °C View Scheme
Multi-step reaction with 13 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 6 h / Reflux 2.1: potassium carbonate / 5 h / 20 °C 3.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 6.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 6.2: 1 h 7.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 8.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 8.2: 0.5 h / -78 °C / Inert atmosphere 8.3: 0.5 h 9.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 9.2: 24 h / 20 °C 10.1: triphenylphosphine / toluene / 3 h / Reflux 11.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 12.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 13.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 13.2: 4 °C View Scheme
Multi-step reaction with 13 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 6 h / Reflux 2.1: potassium carbonate / 5 h / 20 °C 3.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 6.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 6.2: 1 h 7.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 8.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 8.2: 0.5 h / -78 °C / Inert atmosphere 8.3: 0.5 h 9.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 9.2: 3 h / Reflux 10.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 24 h / 20 °C 11.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 12.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 13.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 13.2: 4 °C View Scheme

: (1S,5S,6R)-ethyl 5-(tert-butoxycarbonylamino)-7-azabicyclo[4.1.0]hept-2-ene-3-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 2.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 3.2: 4 °C View Scheme

: 1287204-65-2
(1R,5R)-ethyl 5-hydroxycyclohex-3-enecarboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 11 steps 1.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 4.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 4.2: 1 h 5.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 6.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 6.2: 0.5 h / -78 °C / Inert atmosphere 6.3: 0.5 h 7.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 8.1: triphenylphosphine / toluene / 3 h / Reflux 9.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 10.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 11.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 11.2: 4 °C View Scheme
Multi-step reaction with 10 steps 1.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 4.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 4.2: 1 h 5.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 6.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 6.2: 0.5 h / -78 °C / Inert atmosphere 6.3: 0.5 h 7.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 7.2: 3 h / Reflux 8.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 9.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 10.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.2: 4 °C View Scheme
Multi-step reaction with 11 steps 1.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 4.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 4.2: 1 h 5.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 6.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 6.2: 0.5 h / -78 °C / Inert atmosphere 6.3: 0.5 h 7.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 7.2: 24 h / 20 °C 8.1: triphenylphosphine / toluene / 3 h / Reflux 9.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 10.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 11.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 11.2: 4 °C View Scheme
Multi-step reaction with 11 steps 1.1: triphenylphosphine; diethylazodicarboxylate / toluene / 6 h / -20 °C / Inert atmosphere 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 4.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 4.2: 1 h 5.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 6.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 6.2: 0.5 h / -78 °C / Inert atmosphere 6.3: 0.5 h 7.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 7.2: 3 h / Reflux 8.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 24 h / 20 °C 9.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 10.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 11.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 11.2: 4 °C View Scheme

: 1287204-66-3
(1R,5S)-ethyl 5-(N-(tert-butoxycarbonyl)-4-nitrophenylsulfonamido)cyclohex-3-enecarboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 10 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 3.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 3.2: 1 h 4.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 5.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 5.2: 0.5 h / -78 °C / Inert atmosphere 5.3: 0.5 h 6.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 7.1: triphenylphosphine / toluene / 3 h / Reflux 8.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 9.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 10.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.2: 4 °C View Scheme
Multi-step reaction with 10 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 3.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 3.2: 1 h 4.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 5.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 5.2: 0.5 h / -78 °C / Inert atmosphere 5.3: 0.5 h 6.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 6.2: 3 h / Reflux 7.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 24 h / 20 °C 8.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 9.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 10.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.2: 4 °C View Scheme
Multi-step reaction with 10 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 3.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 3.2: 1 h 4.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 5.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 5.2: 0.5 h / -78 °C / Inert atmosphere 5.3: 0.5 h 6.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 6.2: 24 h / 20 °C 7.1: triphenylphosphine / toluene / 3 h / Reflux 8.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 9.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 10.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.2: 4 °C View Scheme
Multi-step reaction with 9 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; 2-hydroxyethanethiol / acetone / 3 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 3.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 3.2: 1 h 4.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 5.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 5.2: 0.5 h / -78 °C / Inert atmosphere 5.3: 0.5 h 6.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 6.2: 3 h / Reflux 7.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 8.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 9.2: 4 °C View Scheme

: 1287204-67-4
ethyl (5S)-5-((tert-butoxycarbonyl)amino)cyclohex-3-ene-1-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 9 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 2.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 2.2: 1 h 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 4.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 4.2: 0.5 h / -78 °C / Inert atmosphere 4.3: 0.5 h 5.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 6.1: triphenylphosphine / toluene / 3 h / Reflux 7.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 8.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 9.2: 4 °C View Scheme
Multi-step reaction with 8 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 2.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 2.2: 1 h 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 4.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 4.2: 0.5 h / -78 °C / Inert atmosphere 4.3: 0.5 h 5.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 5.2: 3 h / Reflux 6.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 7.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 8.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 8.2: 4 °C View Scheme
Multi-step reaction with 9 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 2.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 2.2: 1 h 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 4.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 4.2: 0.5 h / -78 °C / Inert atmosphere 4.3: 0.5 h 5.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 5.2: 24 h / 20 °C 6.1: triphenylphosphine / toluene / 3 h / Reflux 7.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 8.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 9.2: 4 °C View Scheme
Multi-step reaction with 9 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C 2.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 2.2: 1 h 3.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 4.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 4.2: 0.5 h / -78 °C / Inert atmosphere 4.3: 0.5 h 5.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 5.2: 3 h / Reflux 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 24 h / 20 °C 7.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 8.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 9.2: 4 °C View Scheme

: 1287204-68-5
(1R,3S,5S,6S)-ethyl 5-(tert-butoxycarbonylamino)-7-oxabicyclo[4.1.0]heptane-3-carboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 8 steps 1.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 1.2: 1 h 2.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 3.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 3.2: 0.5 h / -78 °C / Inert atmosphere 3.3: 0.5 h 4.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 5.1: triphenylphosphine / toluene / 3 h / Reflux 6.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 7.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 8.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 8.2: 4 °C View Scheme
Multi-step reaction with 7 steps 1.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 1.2: 1 h 2.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 3.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 3.2: 0.5 h / -78 °C / Inert atmosphere 3.3: 0.5 h 4.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 4.2: 3 h / Reflux 5.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 6.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 7.2: 4 °C View Scheme
Multi-step reaction with 8 steps 1.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 1.2: 1 h 2.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 3.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 3.2: 0.5 h / -78 °C / Inert atmosphere 3.3: 0.5 h 4.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 4.2: 24 h / 20 °C 5.1: triphenylphosphine / toluene / 3 h / Reflux 6.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 7.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 8.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 8.2: 4 °C View Scheme
Multi-step reaction with 8 steps 1.1: titanium(IV) isopropylate; trimethylsilylazide / benzene / 2 h / 5 - 20 °C / Inert atmosphere 1.2: 1 h 2.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 3.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 3.2: 0.5 h / -78 °C / Inert atmosphere 3.3: 0.5 h 4.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 4.2: 3 h / Reflux 5.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 24 h / 20 °C 6.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 7.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 8.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 8.2: 4 °C View Scheme

: 1287204-69-6
(1S,3S,4R,5R)-ethyl 4-azido-3-(tert-butoxycarbonylamino)-5-hydroxycyclohexanecarboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 2.2: 0.5 h / -78 °C / Inert atmosphere 2.3: 0.5 h 3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 4.1: triphenylphosphine / toluene / 3 h / Reflux 5.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 6.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 7.2: 4 °C View Scheme
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 2.2: 0.5 h / -78 °C / Inert atmosphere 2.3: 0.5 h 3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 3.2: 24 h / 20 °C 4.1: triphenylphosphine / toluene / 3 h / Reflux 5.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 6.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 7.2: 4 °C View Scheme

Yield

Multi-step reaction with 7 steps
1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere
2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere
2.2: 0.5 h / -78 °C / Inert atmosphere
2.3: 0.5 h
3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C
4.1: triphenylphosphine / toluene / 3 h / Reflux
5.1: dmap; triethylamine / dichloromethane / 0 - 20 °C
6.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere
7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
7.2: 4 °C
View Scheme

Multi-step reaction with 7 steps
1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere
2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere
2.2: 0.5 h / -78 °C / Inert atmosphere
2.3: 0.5 h
3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C
3.2: 24 h / 20 °C
4.1: triphenylphosphine / toluene / 3 h / Reflux
5.1: dmap; triethylamine / dichloromethane / 0 - 20 °C
6.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere
7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
7.2: 4 °C
View Scheme

: 1287204-70-9
(1S,3S,4S,5S)-ethyl 3-azido-5-(tert-butoxycarbonylamino)-4-hydroxycyclohexanecarboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 2.2: 0.5 h / -78 °C / Inert atmosphere 2.3: 0.5 h 3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 3.2: 3 h / Reflux 4.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 5.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 6.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 6.2: 4 °C View Scheme
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere 2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 2.2: 0.5 h / -78 °C / Inert atmosphere 2.3: 0.5 h 3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 3.2: 3 h / Reflux 4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 24 h / 20 °C 5.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 6.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 7.2: 4 °C View Scheme

Yield

Multi-step reaction with 6 steps
1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere
2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere
2.2: 0.5 h / -78 °C / Inert atmosphere
2.3: 0.5 h
3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C
3.2: 3 h / Reflux
4.1: dmap; triethylamine / dichloromethane / 0 - 20 °C
5.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere
6.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
6.2: 4 °C
View Scheme

Multi-step reaction with 7 steps
1.1: triethylamine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere
2.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere
2.2: 0.5 h / -78 °C / Inert atmosphere
2.3: 0.5 h
3.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C
3.2: 3 h / Reflux
4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / toluene / 24 h / 20 °C
5.1: dmap; triethylamine / dichloromethane / 0 - 20 °C
6.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere
7.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
7.2: 4 °C
View Scheme

: 1287204-71-0
(1S,3S,4R,5R)-ethyl 4-azido-3-(tert-butoxycarbonylamino)-5-(trimethylsilyloxy)cyclohexanecarboxylate

: 204255-11-8
oseltamivir phosphate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 1.2: 0.5 h / -78 °C / Inert atmosphere 1.3: 0.5 h 2.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 3.1: triphenylphosphine / toluene / 3 h / Reflux 4.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 5.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 6.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 6.2: 4 °C View Scheme
Multi-step reaction with 6 steps 1.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere 1.2: 0.5 h / -78 °C / Inert atmosphere 1.3: 0.5 h 2.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C 2.2: 24 h / 20 °C 3.1: triphenylphosphine / toluene / 3 h / Reflux 4.1: dmap; triethylamine / dichloromethane / 0 - 20 °C 5.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere 6.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 6.2: 4 °C View Scheme

Yield

Multi-step reaction with 6 steps
1.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere
1.2: 0.5 h / -78 °C / Inert atmosphere
1.3: 0.5 h
2.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C
3.1: triphenylphosphine / toluene / 3 h / Reflux
4.1: dmap; triethylamine / dichloromethane / 0 - 20 °C
5.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere
6.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
6.2: 4 °C
View Scheme

Multi-step reaction with 6 steps
1.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 0.75 h / -78 °C / Inert atmosphere
1.2: 0.5 h / -78 °C / Inert atmosphere
1.3: 0.5 h
2.1: pyridine; dihydrogen peroxide / dichloromethane / 0.5 h / 20 °C
2.2: 24 h / 20 °C
3.1: triphenylphosphine / toluene / 3 h / Reflux
4.1: dmap; triethylamine / dichloromethane / 0 - 20 °C
5.1: boron trifluoride diethyl etherate / 3 h / -20 °C / Inert atmosphere
6.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
6.2: 4 °C
View Scheme

: 204255-11-8
oseltamivir phosphate

: oseltamivir acid

Conditions

Conditions	Yield
With sodium hydroxide In methanol at 20℃; for 0.5h;	100%
With sodium hydroxide In water at 20℃; for 4h;	96%
Stage #1: oseltamivir phosphate With sodium hydroxide In 1,4-dioxane; water at 20℃; for 24h; Inert atmosphere; Stage #2: In 1,4-dioxane; water Inert atmosphere;	88%

: 204255-11-8
oseltamivir phosphate

: 196618-13-0
oseltamivir

Conditions

Conditions	Yield
With sodium hydrogencarbonate In water at 20℃; for 0.0833333h; Inert atmosphere;	98%
Stage #1: oseltamivir phosphate In dichloromethane; water at 25 - 30℃; for 0.166667h; Stage #2: With ammonia In dichloromethane; water pH=9 - 10; Stage #3: In n-heptane at 25 - 30℃; for 1h; Purification / work up;
Stage #1: oseltamivir phosphate In dichloromethane; water at 25 - 30℃; for 0.166667h; Stage #2: With ammonia In dichloromethane; water pH=9 - 10; Stage #3: In n-heptane; toluene at 20 - 30℃; for 3.5h; Purification / work up;
In dichloromethane; water at 20℃; for 0.75h;

: 24424-99-5
di-tert-butyl dicarbonate

: 204255-11-8
oseltamivir phosphate

: 367252-68-4
(3R,4R,5S)-ethyl 4-acetamido-5-((tert-butoxycarbonyl)amino)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate

Conditions

Conditions	Yield
Stage #1: oseltamivir phosphate With sodium hydrogencarbonate In water Stage #2: di-tert-butyl dicarbonate With triethylamine	98%
Alkaline conditions;	98%
With triethylamine In methanol at 20℃; for 12h;	96.3%

: 152120-54-2, 862686-58-6, 1143572-00-2
N,N'-bis( tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine

: 204255-11-8
oseltamivir phosphate

: ethyl (3R,4R,5S)-4-acetamido-5-[N2,N3-bis(tert-butoxycarbonyl)guanidino]-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate

Conditions

Conditions	Yield
With triethylamine In acetonitrile at 20℃; for 18h;	98%
With amine In tetrahydrofuran

: 145013-05-4
tert-butyl N-({[(tert-butoxy)carbonyl]amino}methanethioyl)carbamate

: 204255-11-8
oseltamivir phosphate

: 208720-81-4
(3R,4R,5S)-5-[[(1Z)-[[(tert-butoxy)carbonyl]amino]([[(tert-butoxy)carbonyl]imino])methyl]amino]-4-acetylamino-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylic acid ethyl ester

Conditions

Conditions	Yield
With triethylamine; mercury dichloride In N,N-dimethyl-formamide at 20℃;	98%

: 34619-03-9
tert-butyldicarbonate

: 204255-11-8
oseltamivir phosphate

: 367252-68-4
(3R,4R,5S)-ethyl 4-acetamido-5-((tert-butoxycarbonyl)amino)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate

Conditions

Conditions	Yield
With triethylamine In methanol at 20℃; for 12h;	96.3%

: 108-24-7
acetic anhydride

: 204255-11-8
oseltamivir phosphate

: 1191921-01-3
(3R,4R,5S)-4-acetylamino-5-acetylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid ethyl ester

Conditions

Conditions	Yield
Stage #1: oseltamivir phosphate With dmap; triethylamine In dichloromethane Stage #2: acetic anhydride In dichloromethane	94%

: 5-(3,5-difluorophenyl)furan-2-carbaldehyde

: 204255-11-8
oseltamivir phosphate

: ethyl (3R,4R,5S)-4-acetamido-5-(((5-(3,5-difluorophenyl)furan-2-yl)methyl)amino)-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate

Conditions

Conditions	Yield
With sodium tris(acetoxy)borohydride In ethanol at 20℃;	89%

: 204255-11-8
oseltamivir phosphate

: C16H28N2O4*H3O4P

Conditions

Conditions	Yield
In ethanol; water at 65 - 75℃; for 8h;	86.9%

: 802294-64-0
propionic acid

: 204255-11-8
oseltamivir phosphate

: (3R,4R,5S)-ethyl 4-acetamido-5-(propionamido)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate

Conditions

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	86%

: 7031-27-8
(phenylthio)acetic acid chloride

: 204255-11-8
oseltamivir phosphate

: C24H34N2O6S

Conditions

Conditions	Yield
With dihydrogen peroxide In acetonitrile at 60℃; for 1h;	86%

: 1623-93-4
4-diphenylsulfonyl chloride

: 204255-11-8
oseltamivir phosphate

: (3R,4R,5S)-5-(([1,1'-biphenyl]-4-sulfonamide))-4-acetamido-3-((pentan-3-yl)oxy)cyclohexene-1-ene-1-carboxylic acid ethyl ester

Conditions

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 6h;	85%
With triethylamine In dichloromethane at 25 - 30℃; for 8h;	84.7%

: 3218-36-8
4-Phenylbenzaldehyde

: 204255-11-8
oseltamivir phosphate

: (3R,4R,5S)-4-acetylamino-5-(([1,1'-biphenyl]-4-ylmethyl)amino)-3-(1-ethylpropyloxy)-1-cyclohexene-1-carboxylic acid ethyl ester

Conditions

Conditions	Yield
With sodium cyanoborohydride In ethanol at 20℃; for 6h;	84%
Stage #1: 4-Phenylbenzaldehyde; oseltamivir phosphate In ethanol at 20℃; for 0.0833333h; Stage #2: With sodium cyanoborohydride In ethanol at 20℃; for 4h;	67%
With sodium cyanoborohydride In ethanol at 20℃; for 6h;

: 5728-52-9
(4-biphenylyl)acetic acid

: 204255-11-8
oseltamivir phosphate

: (3R,4R,5S)-5-(2-([1,1'-biphenyl]-4-yl)acetamido)-4-acetamido-3-((pentan-3-yl)oxy)cyclohexene-1-ene-1-carboxylic acid ethyl ester

Conditions

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 30℃; for 8h;	82.6%

: 98-59-9
p-toluenesulfonyl chloride

: 204255-11-8
oseltamivir phosphate

: ethyl (3R,4R,5S)-4-acetamido-5-((4-methylphenyl)sulfonamido)-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate

Conditions

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 6h;	80%

: 204255-11-8
oseltamivir phosphate

: 501-52-0
3-Phenylpropionic acid

: (3R,4R,5S)-ethyl 4-acetamido-5-(3-phenylpropionamido)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate

Conditions

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	79%

: 204255-11-8
oseltamivir phosphate

: 73217-30-8
3-(chloromethyl)-5-(4-chlorophenyl)-1,2,4-oxadiazole

: C25H33ClN4O5

Conditions

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃; for 12h;	79%

: 62427-25-2
5-(3,4-Dimethoxyphenyl)-2-furaldehyde

: 204255-11-8
oseltamivir phosphate

: ethyl (3R,4R,5S)-4-acetamido-5-(((5-(3,4-dimethoxyphenyl)furan-2-yl)methyl)amino)-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate

Conditions

Conditions	Yield
With sodium tris(acetoxy)borohydride In ethanol at 20℃;	79%

: 98-09-9
benzenesulfonyl chloride

: 204255-11-8
oseltamivir phosphate

: ethyl (3R,4R,5S)-4-acetamido-3-(pentan-3-yloxy)-5-(phenylsulfonamido)cyclohex-1-ene-1-carboxylate

Conditions

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 6h;	79%

: 3446-89-7
4-(Methylthio)benzaldehyde

: 204255-11-8
oseltamivir phosphate

: ethyl (3R,4R,5S)-4-acetamido-3-(sec-butoxy)-5-((4(methylthio)benzyl)amino)cyclohex -1-ene-1-carboxylate

Conditions

Conditions	Yield
With sodium cyanoborohydride In ethanol at 20℃; for 6h;	77.3%

: 498-62-4
3-thiophene carboxaldehyde

: 204255-11-8
oseltamivir phosphate

: ethyl (3R,4R,5S)-4-acetamido-3-(pentan-3-yloxy)-5-((thiophen-3-ylmethyl)amino)cyclohex-1-ene-1-carboxylate

Conditions

Conditions	Yield
With sodium cyanoborohydride In methanol; ethanol at 20℃; for 6h;	77%
With sodium cyanoborohydride In ethanol at 20℃; for 6h;

: 555-16-8
4-nitrobenzaldehdye

: 204255-11-8
oseltamivir phosphate

: (3R,4R,5S)-4-acetamido-5-((4-nitrobenzyl)amino)-3-((pentan-3-yl)oxy)cyclohexene-1-ene-1-carboxylic acid ethyl ester

Conditions

Conditions	Yield
With sodium cyanoborohydride In methanol; ethanol at 20℃; for 6h;	77%
With sodium cyanoborohydride In ethanol at 30℃; for 5h;	76.3%

: 103-82-2
phenylacetic acid

: 204255-11-8
oseltamivir phosphate

: (3R,4R,5S)-ethyl 4-acetamido-5-(phenylacetamido)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate

Conditions

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	77%

: 7031-27-8
(phenylthio)acetic acid chloride

: 204255-11-8
oseltamivir phosphate

: C24H34N2O7S

Conditions

Conditions	Yield
With dihydrogen peroxide In acetonitrile at 60℃; for 24h;	77%

Oseltamivir phosphate History

In Japan, Oseltamivir(204255-11-8) is marketed by Chugai Pharmaceutical Co., which is more than 50% owned by Roche

Oseltamivir phosphate Consensus Reports

Oseltamivir(204255-11-8) acts as a transition-state analogue inhibitor of influenza neuraminidase, preventing progeny virions from detaching from infected cells.

Oseltamivir phosphate Specification

The Oseltamivir phosphate, with its CAS registry number 204255-11-8, has the IUPAC name of ethyl (3R,4R,5S)-4-acetamido-5-amino-3-pentan-3-yloxycyclohexene-1-carboxylate; phosphoric acid. For being a kind of white cyrstalline solid, it is usually applied as an antiviral drug, with its product categories including API; Intermediates & Fine Chemicals; Pharmaceuticals; Ring Systems; Oseltamivir; Influenza Viruses.

The characteristics of this chemical are as below: (1)ACD/LogP: 1.50; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): -1.02; (4)ACD/LogD (pH 7.4): 0.69; (5)ACD/BCF (pH 5.5): 1; (6)ACD/BCF (pH 7.4): 1.25; (7)ACD/KOC (pH 5.5): 1; (8)ACD/KOC (pH 7.4): 24.06; (9)#H bond acceptors: 6; (10)#H bond donors: 3; (11)#Freely Rotating Bonds: 9; (12)Polar Surface Area: 59.08; (13)Flash Point: 240 °C; (14)Enthalpy of Vaporization: 73.64 kJ/mol; (15)Boiling Point: 473.3 °C at 760 mmHg; (16)Vapour Pressure: 3.98E-09 mmHg at 25°C; (17)Exact Mass: 410.181802; (18)MonoIsotopic Mass: 410.181802; (19)Topological Polar Surface Area: 168; (20)Heavy Atom Count: 27; (21)Complexity: 468.

What's more, the following datas could be converted into the molecular structure:
(1)Canonical SMILES: CCC(CC)OC1C=C(CC(C1NC(=O)C)N)C(=O)OCC.OP(=O)(O)O
(2)Isomeric SMILES: CCC(CC)O[C@@H]1C=C(C[C@@H]([C@H]1NC(=O)C)N)C(=O)OCC.OP(=O)(O)O
(3)InChI: InChI=1S/C16H28N2O4.H3O4P/c1-5-12(6-2)22-14-9-11(16(20)21-7-3)8-13(17)15(14)18-10(4)19;1-5(2,3)4/h9,12-15H,5-8,17H2,1-4H3,(H,18,19);(H3,1,2,3,4)/t13-,14+,15+;/m0./s1
(4)InChIKey: PGZUMBJQJWIWGJ-ONAKXNSWSA-N

Product Name

Oseltamivir phosphate

Synthetic route

Oseltamivir phosphate History

Oseltamivir phosphate Consensus Reports

Oseltamivir phosphate Specification

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