Dapagliflozin supplier | CasNO.461432-26-8

Name
Dapagliflozin
EINECS 639-683-0
CAS No. 461432-26-8
Article Data51
CAS DataBase
Density 1.349 g/cm³
Solubility
Melting Point
Formula C₂₁H₂₅ClO₆
Boiling Point 609.045 °C at 760 mmHg
Molecular Weight 408.879
Flash Point 322.139 °C
Transport Information
Appearance
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms BMS 512148;(1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol;D-Glucitol,1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, (1S)-;
PSA 99.38000
LogP 1.84440

Synthetic route

: 461432-25-7
(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With lithium hydroxide In tetrahydrofuran; ethanol	100%
With water; sodium carbonate In methanol at 25 - 50℃; for 6h; Time; Reagent/catalyst;	96.18%
With lithium hydroxide In tetrahydrofuran; methanol; water at 0 - 20℃;	95%

: C21H25ClO6*C3H8O2

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
In n-heptane; tert-butyl methyl ether at -15 - 50℃; Inert atmosphere;	98.7%

: (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-2-ethoxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With triethylsilane; boron trifluoride diethyl etherate In methanol; dichloromethane; acetonitrile at -20 - 20℃; for 5h;	97.3%
With triethylsilane; boron trifluoride diethyl etherate In dichloromethane; acetonitrile at -20 - 0℃; for 5h; Molecular sieve; Inert atmosphere; Large scale; diastereoselective reaction;	79%

: (2R,3R,4R,5S,6S)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)tetrahydro-2H-pyran

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In ethyl acetate at 20℃; for 24h; Autoclave;	97%

: (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol bis(L-proline) cocrystal

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
In water; ethyl acetate at 80℃;	95%
With water In methanol at 20 - 25℃; for 16h;	94%
With water In methanol at 20 - 25℃; for 17h; Reflux;	94%

: (2-chloro-5-((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-2-yl)phenyl)(4-ethoxyphenyl)methanone

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With triethylsilane; boron trifluoride diethyl etherate In dichloromethane; acetonitrile at -25 - 35℃; for 7h; Inert atmosphere;	95%

: (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol bis(L-proline) cocrystal

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Stage #1: (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol bis(L-proline) cocrystal With methanol for 0.333333h; Reflux; Stage #2: With water at 20 - 25℃; for 16.6667h;	94%

: C27H30BrClO8

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With water; potassium hydroxide In acetonitrile at 50 - 60℃; Reagent/catalyst;	91.3%

: 714269-57-5
(2S,3R,4S,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With triethylsilane; boron trifluoride diethyl etherate at 5℃; for 0.00416667h; Temperature;	87.6%
With triethylsilane; aluminum (III) chloride In dichloromethane; acetonitrile at -5 - 10℃; for 3.5h; Large scale;	76%
Stage #1: (2S,3R,4S,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol With aluminum (III) chloride In dichloromethane; acetonitrile at -5℃; for 0.5h; Autoclave; Large scale; Stage #2: With triethylsilane In dichloromethane; acetonitrile at 10℃; for 3h; Large scale;	76%

: 461432-24-6
(3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With triethylsilane; boron trifluoride diethyl etherate In methanol; dichloromethane; ethyl acetate at -20 - 20℃; for 5h;	83.1%
Stage #1: (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol With triethylsilane; boron trifluoride diethyl etherate In dichloromethane; acetonitrile at -10 - 20℃; Stage #2: With water; sodium hydrogencarbonate In dichloromethane; acetonitrile	44%
With triethylsilane; boron trifluoride diethyl etherate In dichloromethane; acetonitrile at -10℃; for 1.5h; Temperature; Time; Inert atmosphere;

: 1103738-29-9
1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene

: tri-n-butyl-(β-D-glucopyranosyl)stannane

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With potassium fluoride; tris-(dibenzylideneacetone)dipalladium(0); bis(3,5-bis(trifluoromethyl)phenyl)(2’,4’,6’-triisopropyl-3,6-dimethoxy-[1,1’-biphenyl]-2-yl)phosphine; copper(l) chloride In 1,4-dioxane at 110℃; for 72h; Inert atmosphere;	82%

: 960404-66-4
L-proline (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyI]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol complex

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With sodium hydrogencarbonate In ethyl acetate at 20℃; for 1.5h;	78%
With sodium hydrogencarbonate In water; ethyl acetate at 30℃; Temperature; Large scale;	6.7 kg

: 864070-37-1
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

: 80-40-0
ethyl ester of p-toluenesulfonic acid

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; caesium carbonate In N,N-dimethyl-formamide at 40℃; for 12h; Inert atmosphere;	75%

: 960494-15-9
C33H57ClO7Si4

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Stage #1: C33H57ClO7Si4 With sodium tetrahydroborate In tetrahydrofuran at -10 - 0℃; Stage #2: With sulfuric acid In tetrahydrofuran at -10 - 20℃; Reagent/catalyst;	60%
Multi-step reaction with 4 steps 1: methanesulfonic acid / tetrahydrofuran; hexane 2: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / -45 - -40 °C 3: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0 - 5 °C 4: sodium hydroxide; water / tetrahydrofuran; methanol / 24 h View Scheme

: C21H23ClO8

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
With triethylsilane; boron trifluoride diethyl etherate In dichloromethane; acetonitrile at -25 - 40℃; for 6h; Inert atmosphere;	55.3%

: (3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-2-ethoxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

A: 461432-26-8
dapagliflozin

B: C21H25ClO6

Conditions

Conditions	Yield
With triethylsilane; boron trifluoride diethyl etherate In dichloromethane; acetonitrile at -15℃; Large scale;	A n/a B 20%

: 281652-58-2
2-chloro-5-iodobenzoylchloride

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C 1.2: 12 h / 0 - 25 °C 1.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C 2.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 2.2: 1 h / -5 - 0 °C 2.3: 16 h / -10 - 20 °C 3.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 0.33 h / -20 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C 1.2: 12 h / 0 - 25 °C 1.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C 2.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 2.2: 1 h / -5 - 0 °C 2.3: 16 h / -10 - 20 °C 3.1: water; ethanol / 0.5 h / Reflux 4.1: methanol / 0.33 h / Reflux 4.2: 16.67 h / 20 - 25 °C View Scheme

Yield

Multi-step reaction with 3 steps
1.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C
1.2: 12 h / 0 - 25 °C
1.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C
2.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere
2.2: 1 h / -5 - 0 °C
2.3: 16 h / -10 - 20 °C
3.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 0.33 h / -20 - 20 °C / Inert atmosphere
View Scheme

Multi-step reaction with 4 steps
1.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C
1.2: 12 h / 0 - 25 °C
1.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C
2.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere
2.2: 1 h / -5 - 0 °C
2.3: 16 h / -10 - 20 °C
3.1: water; ethanol / 0.5 h / Reflux
4.1: methanol / 0.33 h / Reflux
4.2: 16.67 h / 20 - 25 °C
View Scheme

: 103-73-1
Phenetole

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: aluminum (III) chloride / dichloromethane / -10 - 5 °C / Inert atmosphere 2.1: 1,1,3,3-Tetramethyldisiloxane / 5 - 20 °C 3.1: n-butyllithium / tetrahydrofuran; toluene / 0.5 h / -50 - -37 °C / Inert atmosphere 4.1: acetic acid / toluene / -50 - 20 °C / Inert atmosphere 5.1: sodium tetrahydroborate / tetrahydrofuran / -10 - 0 °C 5.2: -10 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: boron trifluoride diethyl etherate; trifluoroacetic anhydride / methanol / 4 h / 35 - 40 °C / Inert atmosphere 1.2: 36 h / Reflux 2.1: n-butyllithium / tetrahydrofuran; toluene; hexane / 1 h / -78 °C / Inert atmosphere 2.2: 3 h / -78 - 75 °C / Inert atmosphere 3.1: trifluoroacetic anhydride / methanol / 20 h / 20 °C 4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 7 h / -25 - 35 °C / Inert atmosphere View Scheme

Yield

Multi-step reaction with 5 steps
1.1: aluminum (III) chloride / dichloromethane / -10 - 5 °C / Inert atmosphere
2.1: 1,1,3,3-Tetramethyldisiloxane / 5 - 20 °C
3.1: n-butyllithium / tetrahydrofuran; toluene / 0.5 h / -50 - -37 °C / Inert atmosphere
4.1: acetic acid / toluene / -50 - 20 °C / Inert atmosphere
5.1: sodium tetrahydroborate / tetrahydrofuran / -10 - 0 °C
5.2: -10 - 20 °C
View Scheme

Multi-step reaction with 4 steps
1.1: boron trifluoride diethyl etherate; trifluoroacetic anhydride / methanol / 4 h / 35 - 40 °C / Inert atmosphere
1.2: 36 h / Reflux
2.1: n-butyllithium / tetrahydrofuran; toluene; hexane / 1 h / -78 °C / Inert atmosphere
2.2: 3 h / -78 - 75 °C / Inert atmosphere
3.1: trifluoroacetic anhydride / methanol / 20 h / 20 °C
4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 7 h / -25 - 35 °C / Inert atmosphere
View Scheme

: 90-80-2
D-Glucono-1,5-lactone

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 4-methyl-morpholine / tetrahydrofuran / 5 - 25 °C / Inert atmosphere 2.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 2.2: 1 h / -5 - 0 °C 2.3: 16 h / -10 - 20 °C 3.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 0.33 h / -20 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: 4-methyl-morpholine / tetrahydrofuran / 5 - 25 °C / Inert atmosphere 2.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 2.2: 1 h / -5 - 0 °C 2.3: 16 h / -10 - 20 °C 3.1: water; ethanol / 0.5 h / Reflux 4.1: methanol / 0.33 h / Reflux 4.2: 16.67 h / 20 - 25 °C View Scheme
Multi-step reaction with 6 steps 1: iodine / dichloromethane / Reflux 2: n-butyllithium / tetrahydrofuran; hexane / -88 - -75 °C / Inert atmosphere 3: methanesulfonic acid / tetrahydrofuran; hexane 4: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / -45 - -40 °C 5: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0 - 5 °C 6: sodium hydroxide; water / tetrahydrofuran; methanol / 24 h View Scheme
Multi-step reaction with 4 steps 1.1: 4-methyl-morpholine / tetrahydrofuran / -20 - 50 °C / Large scale 2.1: n-hexyllithium / tetrahydrofuran; toluene / -100 - -80 °C / Large scale 2.2: -105 - -80 °C / Large scale 2.3: 3 h / -100 - 20 °C / Large scale 3.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / -35 - 20 °C / Inert atmosphere; Large scale 3.2: 35 - 40 °C / Large scale 4.1: water; Isopropyl acetate / 20 - 45 °C / Large scale View Scheme
Multi-step reaction with 4 steps 1.1: 4-methyl-morpholine / tetrahydrofuran / 0 °C / Large scale 1.2: 17 h / Large scale 2.1: n-butyllithium / tetrahydrofuran; toluene; hexane / 0.5 h / -80 - -78 °C / Inert atmosphere; Large scale 2.2: 1 h / Cooling; Large scale 2.3: 2 h / -30 - 15 °C / Large scale 3.1: methanesulfonic acid / 9 h / 15 - 40 °C / Large scale 4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 5 h / -20 - 0 °C / Molecular sieve; Inert atmosphere; Large scale View Scheme

: 19094-56-5
2-chloro-5-iodobenzoic acid

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 16.17 h / 10 - 25 °C 2.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C 2.2: 12 h / 0 - 25 °C 2.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C 3.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 3.2: 1 h / -5 - 0 °C 3.3: 16 h / -10 - 20 °C 4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 0.33 h / -20 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 16.17 h / 10 - 25 °C 2.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C 2.2: 12 h / 0 - 25 °C 2.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C 3.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 3.2: 1 h / -5 - 0 °C 3.3: 16 h / -10 - 20 °C 4.1: water; ethanol / 0.5 h / Reflux 5.1: methanol / 0.33 h / Reflux 5.2: 16.67 h / 20 - 25 °C View Scheme

Yield

Multi-step reaction with 4 steps
1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 16.17 h / 10 - 25 °C
2.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C
2.2: 12 h / 0 - 25 °C
2.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C
3.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere
3.2: 1 h / -5 - 0 °C
3.3: 16 h / -10 - 20 °C
4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 0.33 h / -20 - 20 °C / Inert atmosphere
View Scheme

Multi-step reaction with 5 steps
1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 16.17 h / 10 - 25 °C
2.1: aluminum (III) chloride / dichloromethane / 0.5 h / -3 - 5 °C
2.2: 12 h / 0 - 25 °C
2.3: polymethylhydrosiloxane (PMHS) / 16 h / 30 °C
3.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere
3.2: 1 h / -5 - 0 °C
3.3: 16 h / -10 - 20 °C
4.1: water; ethanol / 0.5 h / Reflux
5.1: methanol / 0.33 h / Reflux
5.2: 16.67 h / 20 - 25 °C
View Scheme

: 1103738-29-9
1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 1.2: 1 h / -5 - 0 °C 1.3: 16 h / -10 - 20 °C 2.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 0.33 h / -20 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 1.2: 1 h / -5 - 0 °C 1.3: 16 h / -10 - 20 °C 2.1: water; ethanol / 0.5 h / Reflux 3.1: methanol / 0.33 h / Reflux 3.2: 16.67 h / 20 - 25 °C View Scheme

: 32469-28-6, 55515-28-1, 55515-29-2, 32384-65-9
(3R,4S,5R,6R)-3,4,5-tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-2-one

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 1.2: 1 h / -5 - 0 °C 1.3: 16 h / -10 - 20 °C 2.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 0.33 h / -20 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: TurboGrignard / tetrahydrofuran / 1.5 h / -5 - 0 °C / Inert atmosphere 1.2: 1 h / -5 - 0 °C 1.3: 16 h / -10 - 20 °C 2.1: water; ethanol / 0.5 h / Reflux 3.1: methanol / 0.33 h / Reflux 3.2: 16.67 h / 20 - 25 °C View Scheme
Multi-step reaction with 5 steps 1: n-butyllithium / tetrahydrofuran; hexane / -88 - -75 °C / Inert atmosphere 2: methanesulfonic acid / tetrahydrofuran; hexane 3: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / -45 - -40 °C 4: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0 - 5 °C 5: sodium hydroxide; water / tetrahydrofuran; methanol / 24 h View Scheme

: 864070-19-9
[4-(5-bromo-2-chloro-benzyl)-phenoxy]-tert-butyl-dimethyl-silane

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere 1.2: 3 h / -65 - -55 °C 1.3: 16 h / 20 - 25 °C 2.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere 3.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere View Scheme

Yield

Multi-step reaction with 3 steps
1.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere
1.2: 3 h / -65 - -55 °C
1.3: 16 h / 20 - 25 °C
2.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere
3.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere
View Scheme

: 1204220-63-2
(2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere 2: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere View Scheme

: 21739-92-4
5-bromo-2-chlorobenzoic acid

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 8 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 10 h / 20 °C 2.1: aluminum (III) chloride / dichloromethane / 1 h / -5 - 20 °C / Inert atmosphere 2.2: 2 h / -5 - 0 °C / Inert atmosphere 3.1: aluminum (III) chloride; sodium tetrahydroborate / tetrahydrofuran / 18 h / 5 - 20 °C / Inert atmosphere 4.1: boron tribromide / dichloromethane / -10 - 0 °C / Inert atmosphere 5.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C 6.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere 6.2: 3 h / -65 - -55 °C 6.3: 16 h / 20 - 25 °C 7.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere 8.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1.1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 2 h / Reflux 2.1: aluminum (III) chloride / dichloromethane / 1 h / Ca. -12 - Ca.-8 °C / Inert atmosphere 3.1: triethylsilane / dichloromethane / 0.3 h / 0 - 15 °C 4.1: 1,1,1,3,3,3-hexamethyl-disilazane / dichloromethane / Reflux 4.2: -85 - -75 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0 - 5 °C 6.1: sodium hydroxide; water / tetrahydrofuran; methanol / 24 h View Scheme
Multi-step reaction with 8 steps 1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 2 h / Reflux 2: aluminum (III) chloride / dichloromethane / 1 h / Ca. -12 - Ca.-8 °C / Inert atmosphere 3: triethylsilane / dichloromethane / 0.3 h / 0 - 15 °C 4: n-butyllithium / tetrahydrofuran; hexane / -88 - -75 °C / Inert atmosphere 5: methanesulfonic acid / tetrahydrofuran; hexane 6: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / -45 - -40 °C 7: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0 - 5 °C 8: sodium hydroxide; water / tetrahydrofuran; methanol / 24 h View Scheme
Multi-step reaction with 4 steps 1.1: boron trifluoride diethyl etherate; trifluoroacetic anhydride / methanol / 4 h / 35 - 40 °C / Inert atmosphere 1.2: 36 h / Reflux 2.1: n-butyllithium / tetrahydrofuran; toluene; hexane / 1 h / -78 °C / Inert atmosphere 2.2: 3 h / -78 - 75 °C / Inert atmosphere 3.1: trifluoroacetic anhydride / methanol / 20 h / 20 °C 4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 7 h / -25 - 35 °C / Inert atmosphere View Scheme

: 21900-52-7
5-bromo-2-chloro-benzoyl chloride

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 7 steps 1.1: aluminum (III) chloride / dichloromethane / 1 h / -5 - 20 °C / Inert atmosphere 1.2: 2 h / -5 - 0 °C / Inert atmosphere 2.1: aluminum (III) chloride; sodium tetrahydroborate / tetrahydrofuran / 18 h / 5 - 20 °C / Inert atmosphere 3.1: boron tribromide / dichloromethane / -10 - 0 °C / Inert atmosphere 4.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C 5.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere 5.2: 3 h / -65 - -55 °C 5.3: 16 h / 20 - 25 °C 6.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere 7.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: aluminum (III) chloride / dichloromethane / 1 h / Ca. -12 - Ca.-8 °C / Inert atmosphere 2.1: triethylsilane / dichloromethane / 0.3 h / 0 - 15 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / dichloromethane / Reflux 3.2: -85 - -75 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0 - 5 °C 5.1: sodium hydroxide; water / tetrahydrofuran; methanol / 24 h View Scheme
Multi-step reaction with 7 steps 1: aluminum (III) chloride / dichloromethane / 1 h / Ca. -12 - Ca.-8 °C / Inert atmosphere 2: triethylsilane / dichloromethane / 0.3 h / 0 - 15 °C 3: n-butyllithium / tetrahydrofuran; hexane / -88 - -75 °C / Inert atmosphere 4: methanesulfonic acid / tetrahydrofuran; hexane 5: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / -45 - -40 °C 6: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0 - 5 °C 7: sodium hydroxide; water / tetrahydrofuran; methanol / 24 h View Scheme
Multi-step reaction with 5 steps 1.1: aluminum (III) chloride / dichloromethane / -10 - 5 °C / Inert atmosphere 2.1: 1,1,3,3-Tetramethyldisiloxane / 5 - 20 °C 3.1: n-butyllithium / tetrahydrofuran; toluene / 0.5 h / -50 - -37 °C / Inert atmosphere 4.1: acetic acid / toluene / -50 - 20 °C / Inert atmosphere 5.1: sodium tetrahydroborate / tetrahydrofuran / -10 - 0 °C 5.2: -10 - 20 °C View Scheme

: 333361-49-2
(5-bromo-2-chlorophenyl)(4-methoxyphenyl)methanone

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: aluminum (III) chloride; sodium tetrahydroborate / tetrahydrofuran / 18 h / 5 - 20 °C / Inert atmosphere 2.1: boron tribromide / dichloromethane / -10 - 0 °C / Inert atmosphere 3.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C 4.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere 4.2: 3 h / -65 - -55 °C 4.3: 16 h / 20 - 25 °C 5.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere 6.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere View Scheme

Yield

Multi-step reaction with 6 steps
1.1: aluminum (III) chloride; sodium tetrahydroborate / tetrahydrofuran / 18 h / 5 - 20 °C / Inert atmosphere
2.1: boron tribromide / dichloromethane / -10 - 0 °C / Inert atmosphere
3.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C
4.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere
4.2: 3 h / -65 - -55 °C
4.3: 16 h / 20 - 25 °C
5.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere
6.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere
View Scheme

: 4-bromo-1-chloro-2-(4-methoxybenzyl)benzene

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: boron tribromide / dichloromethane / -10 - 0 °C / Inert atmosphere 2.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C 3.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere 3.2: 3 h / -65 - -55 °C 3.3: 16 h / 20 - 25 °C 4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere 5.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere View Scheme

Yield

Multi-step reaction with 5 steps
1.1: boron tribromide / dichloromethane / -10 - 0 °C / Inert atmosphere
2.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C
3.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere
3.2: 3 h / -65 - -55 °C
3.3: 16 h / 20 - 25 °C
4.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere
5.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere
View Scheme

: 864070-18-8
4-(5-bromo-2-chlorobenzyl)phenol

: 461432-26-8
dapagliflozin

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C 2.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere 2.2: 3 h / -65 - -55 °C 2.3: 16 h / 20 - 25 °C 3.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere 4.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere View Scheme

Yield

Multi-step reaction with 4 steps
1.1: triethylamine / acetonitrile / 2 h / 5 - 15 °C
2.1: n-butyllithium / tetrahydrofuran; hexane; toluene / 0.5 h / -65 °C / Inert atmosphere
2.2: 3 h / -65 - -55 °C
2.3: 16 h / 20 - 25 °C
3.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane; acetonitrile / 2 h / -30 - -10 °C / Inert atmosphere
4.1: caesium carbonate; tetra-(n-butyl)ammonium iodide / N,N-dimethyl-formamide / 12 h / 40 °C / Inert atmosphere
View Scheme

: 461432-26-8
dapagliflozin

: 1125-88-8
benzaldehyde dimethyl acetal

: (4aR,6S,7R,8R,8aS)-6-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-2-phenyl-4,4a,6,7,8,8a-hexahydro-2H-pyrano[3,2-d][1,3]dioxine-7,8-diol

Conditions

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile at 20℃; for 0.333333h;	99%
With toluene-4-sulfonic acid In acetonitrile at 20℃; for 0.333333h;	98.7%
With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 100℃; Inert atmosphere;	95%

: 461432-26-8
dapagliflozin

: 108-24-7
acetic anhydride

: 18162-48-6
tert-butyldimethylsilyl chloride

: C33H45ClO8Si

Conditions

Conditions	Yield
Stage #1: dapagliflozin; tert-butyldimethylsilyl chloride With dmap In pyridine at 20℃; Cooling with ice; Stage #2: acetic anhydride In pyridine at 20℃; for 3h;	92%

...Expand

: 461432-26-8
dapagliflozin

: 64-17-5
ethanol

: dapagliflozin hemiethanolate

Conditions

Conditions	Yield
In 2,2,4-trimethylpentane at 0 - 10℃; Solvent;	92%

: 461432-26-8
dapagliflozin

: 74-79-3
L-arginine

: C21H25ClO6*C6H14N4O2

Conditions

Conditions	Yield
In methanol at 15 - 40℃; for 6.5h; Solvent;	90%

: 461432-26-8
dapagliflozin

: 98-59-9
p-toluenesulfonyl chloride

: 1219000-33-5
((2R,3S,4R,5R,6S)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl 4-methylbenzenesulfonate

Conditions

Conditions	Yield
With pyridine at 0℃; for 2h;	88%
With 2,6-dimethylpyridine at 0 - 20℃;
With 2,6-dimethylpyridine at 0 - 20℃; for 6h;

: 110-85-0
piperazine

: 461432-26-8
dapagliflozin

: C21H25ClO6*C4H10N2

Conditions

Conditions	Yield
In toluene for 1h; Solvent; Reflux; Dean-Stark;	88%

: 461432-26-8
dapagliflozin

: 108-24-7
acetic anhydride

: 461432-25-7
(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

Conditions

Conditions	Yield
With pyridine; dmap at 20℃; for 2h; Cooling with ice;	87%
With dmap In acetone at 20 - 30℃; for 3h; Solvent; Temperature; Concentration;	6.4g
Stage #1: dapagliflozin With dmap In dichloromethane at 25 - 30℃; for 0.333333h; Stage #2: acetic anhydride In dichloromethane at 25 - 30℃; for 4h;	128 g
With 4-methyl-morpholine; dmap In dichloromethane at 0 - 25℃; for 16h;	515 g

: 461432-26-8
dapagliflozin

: 85272-31-7
di-tert-butylsilyl bis(trifluoromethanesulfonate)

: (4aR,6S,7R,8R,8aS)-2,2-di-tert-butyl-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)hexahydropyrano[3,2-d][1,3,2]dioxasiline-7,8-diol

Conditions

Conditions	Yield
With 2,6-dimethylpyridine In dichloromethane at 0℃; for 0.5h; Inert atmosphere;	85%

: 461432-26-8
dapagliflozin

: 1125-88-8
benzaldehyde dimethyl acetal

: 1181680-65-8
C28H29ClO6

Conditions

Conditions	Yield
With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 60℃;	83%
With camphor-10-sulfonic acid In N,N-dimethyl-formamide at 110℃; for 3h; Inert atmosphere;

: 461432-26-8
dapagliflozin

: 147-85-3
L-proline

: (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol bis(L-proline) cocrystal

Conditions

Conditions	Yield
In ethanol; water for 0.5h; Reflux;	66%
In water; isopropyl alcohol at 20 - 80℃;
In ethanol; water for 0.5h; Reflux;	3.8 g
In ethanol; hexane; water at 20℃; for 17h; Temperature; Time; Solvent; Reflux;	3.8 g

: 461432-26-8
dapagliflozin

: (2S,3S,5R,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-3,5-dihydroxy-6-(hydroxymethyl)dihydro-2H-pyran-4(3H)-one

Conditions

Conditions	Yield
With [(neocuproine)Pd(μ-OAc)]2(OTf)2; oxygen In water; acetonitrile at 20℃; for 48h; Reagent/catalyst;	51%
Multi-step reaction with 6 steps 1: camphor-10-sulfonic acid / N,N-dimethyl-formamide / 60 °C 2: 1H-imidazole / N,N-dimethyl-formamide; dichloromethane / 20 °C / Cooling with ice 3: N-ethyl-N,N-diisopropylamine / Reflux 4: tetrabutyl ammonium fluoride / tetrahydrofuran / 6 h / 20 °C 5: acetic anhydride / dimethyl sulfoxide / 20 °C / Cooling with ice 6: camphor-10-sulfonic acid / methanol / 60 °C View Scheme

Yield

With [(neocuproine)Pd(μ-OAc)]2(OTf)2; oxygen In water; acetonitrile at 20℃; for 48h; Reagent/catalyst;

51%

Multi-step reaction with 6 steps
1: camphor-10-sulfonic acid / N,N-dimethyl-formamide / 60 °C
2: 1H-imidazole / N,N-dimethyl-formamide; dichloromethane / 20 °C / Cooling with ice
3: N-ethyl-N,N-diisopropylamine / Reflux
4: tetrabutyl ammonium fluoride / tetrahydrofuran / 6 h / 20 °C
5: acetic anhydride / dimethyl sulfoxide / 20 °C / Cooling with ice
6: camphor-10-sulfonic acid / methanol / 60 °C
View Scheme

: 461432-26-8
dapagliflozin

: 110-17-8
(2E)-but-2-enedioic acid

: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol fumarate

Conditions

Conditions	Yield
In ethanol; water at 4 - 50℃; for 19h;	46%
In water Solvent; Reflux;	1.1 g

: 461432-26-8
dapagliflozin

: 69-65-8
mannitol

: dapagliflozin D-mannitol hydrate

Conditions

Conditions	Yield
In ethanol; water at 80℃; for 3h;	45%

: 461432-26-8
dapagliflozin

: 864070-37-1
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

Conditions

Conditions	Yield
With boron tribromide In dichloromethane at -78 - 20℃;	38%
With hydrogen bromide In water for 16h; Reflux;	1.6 g

: 461432-26-8
dapagliflozin

: 75-36-5
acetyl chloride

: ((2R,3S,4R,5R,6S)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate

Conditions

Conditions	Yield
With pyridine at -40 - -30℃; for 4h; Inert atmosphere;	33%

Dapagliflozin Specification

The Dapagliflozin, with the CAS registry number 461432-26-8, is also known as (1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol. It belongs to the product categories of Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals.This chemical's molecular formula is C₂₁H₂₅ClO₆ and molecular weight is 408.87.Its EINECS number is 204-115-9. What's more,Its systematic name is D-Glucitol,1,5-anhydro-1-C-(4-chloro-3-((4-ethoxyphenyl)methyl)phenyl)-,(1S)-.It is one kind of white crystalline powder, odorless, little bitter taste.And it is the treatment of type 1 or type 2 diabetes, or any condition causing hyperglycemia.

Physical properties about Dapagliflozin are:
(1)ACD/LogP: 2.09; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): 2.09; (4)ACD/LogD (pH 7.4): 2.09; (5)ACD/BCF (pH 5.5): 22.83; (6)ACD/BCF (pH 7.4): 22.83; (7)ACD/KOC (pH 5.5): 326.57; (8)ACD/KOC (pH 7.4): 326.57; (9)#H bond acceptors: 6; (10)#H bond donors: 4; (11)#Freely Rotating Bonds: 10; (12)Index of Refraction: 1.614; (13)Molar Refractivity: 105.629 cm³ ; (14)Molar Volume: 303.074 cm³; (15)Surface Tension: 54.3219985961914 dyne/cm; (16)Density: 1.349 g/cm³; (17)Flash Point: 322.139 °C; (18)Enthalpy of Vaporization: 95.131 kJ/mol; (19)Boiling Point: 609.045 °C at 760 mmHg; (20)Vapour Pressure: 0 mmHg at 25°C.

You can still convert the following datas into molecular structure:
(1)SMILES:Clc1ccc(cc1Cc2ccc(OCC)cc2)[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O;
(2)Std. InChI:InChI=1S/C21H25ClO6/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21/h3-8,10,17-21,23-26H,2,9,11H2,1H3/t17-,18-,19+,20-,21+/m1/s1;
(3)Std. InChIKey:JVHXJTBJCFBINQ-ADAARDCZSA-N.

Product Name

Dapagliflozin

Synthetic route

Dapagliflozin Specification

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