Licofelone supplier | CasNO.156897-06-2

Name
Licofelone
EINECS 694-581-3
CAS No. 156897-06-2
Article Data10
CAS DataBase
Density 1.23 g/cm³
Solubility
Melting Point 162-163 °C
Formula C₂₃H₂₂ClNO₂
Boiling Point 539.7 °C at 760 mmHg
Molecular Weight 379.886
Flash Point 280.2 °C
Transport Information
Appearance Yellowish solid
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms ML 3000;[2,2-Dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]aceticacid;
PSA 42.23000
LogP 5.68490

Synthetic route

: 156897-35-7
ethyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate

: 156897-06-2
licofelone

Conditions

Conditions	Yield
With sodium hydroxide In ethanol; water at 80℃;	77%
With sodium hydroxide In ethanol at 80℃; for 0.25h;	77%
With sodium hydroxide In ethanol for 0.166667h; Heating;	75.5%
Stage #1: ethyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate With sodium hydroxide; water In ethanol for 0.5h; Heating / reflux; Stage #2: With hydrogenchloride In ethanol; water Product distribution / selectivity;	64%
With aq. alkaline hydroxide at 60 - 70℃; for 1h;

: 1061179-20-1
methyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetate

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Stage #1: methyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetate With sodium hydroxide; water In ethanol for 0.5h; Heating / reflux; Stage #2: With hydrogenchloride In ethanol; water Product distribution / selectivity;	71%
With aq. alkaline hydroxide at 60 - 70℃; for 1h;

: 262426-70-0
[6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizin-5-yl]acetic acid tert-butyl ester

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Stage #1: [6-(4-chlorophenyl)-2,3-dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizin-5-yl]acetic acid tert-butyl ester With sodium hydroxide; water In ethanol for 8h; Heating / reflux; Stage #2: With hydrogenchloride In ethanol; water Product distribution / selectivity;	60%
With aq. alkaline hydroxide at 60 - 70℃; for 10h;

: C23H20ClNO3

: 156897-06-2
licofelone

Conditions

Conditions	Yield
With hydrazine hydrate; potassium hydroxide In ethylene diglycol at 85 - 145℃; for 7h; Wolff-Kishner reduction;	55%
With hydrazine hydrate; potassium hydroxide In diethylene glycol at 85 - 145℃; for 7h; Wolff-Kishner reduction;	55%
With hydrazine hydrate; potassium hydroxide In diethylene glycol at 50 - 145℃; Wolff-Kishner reduction;	55.6%

: 1061179-22-3
2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetamide

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Stage #1: 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetamide With sulfuric acid; water In methanol for 4h; Heating / reflux; Stage #2: With sodium hydroxide; water In methanol for 4h; Heating / reflux; Stage #3: With hydrogenchloride In methanol; water Product distribution / selectivity;	50%

: 3355-31-5
1-chloro-3-phenyl-2-propyne

(1,2-dimethyl-3-zirconacyclopent-1-ene)(C5H5)2: (1,2-dimethyl-3-zirconacyclopent-1-ene)(C5H5)2

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 8 steps 1: 90 percent / aq. NaOH, NaI, n-Bu4NI / toluene / 24 h / 50 °C 2: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 3: 68 percent / pivalic acid / 5 h / 150 °C 4: 77 percent / EtONa / ethanol / 15 h / Ambient temperature 5: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h 6: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h 7: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h 8: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C View Scheme

Yield

Multi-step reaction with 8 steps
1: 90 percent / aq. NaOH, NaI, n-Bu4NI / toluene / 24 h / 50 °C
2: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h
3: 68 percent / pivalic acid / 5 h / 150 °C
4: 77 percent / EtONa / ethanol / 15 h / Ambient temperature
5: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h
6: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h
7: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h
8: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C
View Scheme

: 197963-29-4
2,2-dimethyl-5-phenylpent-4-ynal

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 7 steps 1: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h 2: 68 percent / pivalic acid / 5 h / 150 °C 3: 77 percent / EtONa / ethanol / 15 h / Ambient temperature 4: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h 5: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h 6: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h 7: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C View Scheme
Multi-step reaction with 7 steps 1: 80 percent / NaBH(OAc)3, Et3N / CH2Cl2 / Ambient temperature 2: 68 percent / t-BuCO2H / 150 °C 3: 77 percent / EtONa / ethanol / Ambient temperature 4: 80 percent / NaH / tetrahydrofuran / Ambient temperature 5: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating 6: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux 7: 77 percent / NaOH / ethanol; H2O / 80 °C View Scheme

Yield

Multi-step reaction with 7 steps
1: 1.) Et3N, 2.) NaBH(OAc)3 / 1) CH2Cl2, rt, 15 min; 2) CH2Cl2, rt, 12 h
2: 68 percent / pivalic acid / 5 h / 150 °C
3: 77 percent / EtONa / ethanol / 15 h / Ambient temperature
4: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h
5: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h
6: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h
7: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C
View Scheme

Multi-step reaction with 7 steps
1: 80 percent / NaBH(OAc)3, Et3N / CH2Cl2 / Ambient temperature
2: 68 percent / t-BuCO2H / 150 °C
3: 77 percent / EtONa / ethanol / Ambient temperature
4: 80 percent / NaH / tetrahydrofuran / Ambient temperature
5: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating
6: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux
7: 77 percent / NaOH / ethanol; H2O / 80 °C
View Scheme

: 197963-31-8
2,2-dimethyl-7-phenyl-2,3,5,6-tetrahydro-1H-pyrrolizin-6-one

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: 77 percent / EtONa / ethanol / 15 h / Ambient temperature 2: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h 3: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h 4: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h 5: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C View Scheme
Multi-step reaction with 5 steps 1: 77 percent / EtONa / ethanol / Ambient temperature 2: 80 percent / NaH / tetrahydrofuran / Ambient temperature 3: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating 4: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux 5: 77 percent / NaOH / ethanol; H2O / 80 °C View Scheme

: 197963-30-7
methyl N-(2,2-dimethyl-5-phenylpent-4-ynyl)glycinate

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: 68 percent / pivalic acid / 5 h / 150 °C 2: 77 percent / EtONa / ethanol / 15 h / Ambient temperature 3: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h 4: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h 5: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h 6: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C View Scheme
Multi-step reaction with 6 steps 1: 68 percent / t-BuCO2H / 150 °C 2: 77 percent / EtONa / ethanol / Ambient temperature 3: 80 percent / NaH / tetrahydrofuran / Ambient temperature 4: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating 5: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux 6: 77 percent / NaOH / ethanol; H2O / 80 °C View Scheme

Yield

Multi-step reaction with 6 steps
1: 68 percent / pivalic acid / 5 h / 150 °C
2: 77 percent / EtONa / ethanol / 15 h / Ambient temperature
3: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h
4: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h
5: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h
6: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C
View Scheme

Multi-step reaction with 6 steps
1: 68 percent / t-BuCO2H / 150 °C
2: 77 percent / EtONa / ethanol / Ambient temperature
3: 80 percent / NaH / tetrahydrofuran / Ambient temperature
4: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating
5: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux
6: 77 percent / NaOH / ethanol; H2O / 80 °C
View Scheme

: 197963-32-9
ethyl 2-(2,2-dimethyl-6-hydroxy-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)-2-oxoacetate

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) NaH / 1) THF, rt, 1 h; 2) THF, rt, 12 h 2: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h 3: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h 4: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C View Scheme
Multi-step reaction with 4 steps 1: 80 percent / NaH / tetrahydrofuran / Ambient temperature 2: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating 3: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux 4: 77 percent / NaOH / ethanol; H2O / 80 °C View Scheme

: 197963-34-1
ethyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)-2-oxoacetate

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h 2: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux 2: 77 percent / NaOH / ethanol; H2O / 80 °C View Scheme

: 197963-33-0
ethyl 2-(2,2-dimethyl-7-phenyl-6-trifluoromethanesulfonyloxy-2,3-dihydro-1H-pyrrolizin-5-yl)-2-oxoacetate

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / Pd(PPh3)4, Na2CO3 / tetrahydrofuran; H2O / 1) rt, 1 h; 2) reflux, 1 h 2: 1.) p-toluenesulfonhydrazide, p-TsOH*H2O, 2.) NaBH3CN / 1) EtOH, reflux, 7 h; 2) EtOH, reflux, 4 h 3: 77 percent / aq. NaOH / ethanol / 0.25 h / 80 °C View Scheme
Multi-step reaction with 3 steps 1: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating 2: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux 3: 77 percent / NaOH / ethanol; H2O / 80 °C View Scheme

: 3355-31-5
1-chloro-3-phenyl-2-propyne

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 8 steps 1: 90 percent / n-Bu4NI, NaI, NaOH / H2O; toluene / 50 °C 2: 80 percent / NaBH(OAc)3, Et3N / CH2Cl2 / Ambient temperature 3: 68 percent / t-BuCO2H / 150 °C 4: 77 percent / EtONa / ethanol / Ambient temperature 5: 80 percent / NaH / tetrahydrofuran / Ambient temperature 6: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating 7: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux 8: 77 percent / NaOH / ethanol; H2O / 80 °C View Scheme

Yield

Multi-step reaction with 8 steps
1: 90 percent / n-Bu4NI, NaI, NaOH / H2O; toluene / 50 °C
2: 80 percent / NaBH(OAc)3, Et3N / CH2Cl2 / Ambient temperature
3: 68 percent / t-BuCO2H / 150 °C
4: 77 percent / EtONa / ethanol / Ambient temperature
5: 80 percent / NaH / tetrahydrofuran / Ambient temperature
6: 92 percent / Pd(PPh3)4, Na2CO3 / H2O; tetrahydrofuran / Heating
7: 1.) p-toluenesulfonyl hydrazide, p-TsOH, 2.) NaBH3CN / 1.) EtOH, reflux, 2.) EtOH, reflux
8: 77 percent / NaOH / ethanol; H2O / 80 °C
View Scheme

: 536-38-9
4-chlorobenzoylmethyl bromide

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHCO3 / diethyl ether; ethanol; H2O / 36 h / Ambient temperature 2: Cu / toluene / 0.25 h / Heating 3: 75.5 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme
Multi-step reaction with 3 steps 1.1: ethanol / 0.5 h 2.1: tetrahydrofuran / 18 - 25 °C / Inert atmosphere 2.2: 0.33 h / 25 - 30 °C 3.1: hydrazine hydrate; potassium hydroxide / diethylene glycol / 50 - 145 °C View Scheme

: 116673-95-1
5-benzyl-3,3-dimethyl-3,4-dihydro-2H-pyrrole

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: NaHCO3 / diethyl ether; ethanol; H2O / 36 h / Ambient temperature 2: Cu / toluene / 0.25 h / Heating 3: 75.5 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydrogencarbonate / ethanol / 36 h / 20 °C 2.1: tetrahydrofuran / 10 - 15 °C 2.2: 0.33 h / 25 - 30 °C 3.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 4 steps 1: sodium hydrogencarbonate / ethanol; water / 36 h / 20 °C 2: tetrahydrofuran / 10 - 15 °C 3: water / tetrahydrofuran / 0.33 h / 25 - 30 °C 4: hydrazine hydrate; potassium hydroxide / diethylene glycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 3 steps 1.1: ethanol / 0.5 h 2.1: tetrahydrofuran / 18 - 25 °C / Inert atmosphere 2.2: 0.33 h / 25 - 30 °C 3.1: hydrazine hydrate; potassium hydroxide / diethylene glycol / 50 - 145 °C View Scheme

: 133111-56-5
2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: Cu / toluene / 0.25 h / Heating 2: 75.5 percent / 10percent aq. NaOH / ethanol / 0.17 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 10 - 15 °C 1.2: 0.33 h / 25 - 30 °C 2.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 3 steps 1: tetrahydrofuran / 10 - 15 °C 2: water / tetrahydrofuran / 0.33 h / 25 - 30 °C 3: hydrazine hydrate; potassium hydroxide / diethylene glycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 18 - 25 °C / Inert atmosphere 1.2: 0.33 h / 25 - 30 °C 2.1: hydrazine hydrate; potassium hydroxide / diethylene glycol / 50 - 145 °C View Scheme

: 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-ylacetic acid toluene solvate

: 156897-06-2
licofelone

Conditions

Conditions	Yield
In methanol; ethyl acetate at 0 - 5℃; for 5h;

: 79-37-8
oxalyl dichloride

: 133111-56-5
2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Stage #1: oxalyl dichloride; 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine In tetrahydrofuran at 10 - 25℃; for 0.5 - 0.75h; Stage #2: With water In tetrahydrofuran at 0 - 30℃; for 0.0833333 - 0.166667h; Stage #3: With hydrogenchloride; potassium hydroxide; hydrazine more than 3 stages;

: 1003-85-6
5.5-dimethyl-1,3,2-dioxathiane-2-oxide

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: dimethyl sulfoxide / 36 h / 100 °C 2.1: pyridine; thionyl chloride / 0 °C 3.1: diethyl ether / 2 h / Reflux 3.2: 3 h / Reflux 4.1: sodium hydrogencarbonate / ethanol / 36 h / 20 °C 5.1: tetrahydrofuran / 10 - 15 °C 5.2: 0.33 h / 25 - 30 °C 6.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme

: 103804-80-4
3,3-dimethyl-4-hydroxy butyronitrile

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: pyridine; thionyl chloride / 0 °C 2.1: diethyl ether / 2 h / Reflux 2.2: 3 h / Reflux 3.1: sodium hydrogencarbonate / ethanol / 36 h / 20 °C 4.1: tetrahydrofuran / 10 - 15 °C 4.2: 0.33 h / 25 - 30 °C 5.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme

: 126-30-7
2,2-Dimethyl-1,3-propanediol

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 7 steps 1.1: thionyl chloride / dichloromethane / 5 - 10 °C 2.1: dimethyl sulfoxide / 36 h / 100 °C 3.1: pyridine; thionyl chloride / 0 °C 4.1: diethyl ether / 2 h / Reflux 4.2: 3 h / Reflux 5.1: sodium hydrogencarbonate / ethanol / 36 h / 20 °C 6.1: tetrahydrofuran / 10 - 15 °C 6.2: 0.33 h / 25 - 30 °C 7.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme

Yield

Multi-step reaction with 7 steps
1.1: thionyl chloride / dichloromethane / 5 - 10 °C
2.1: dimethyl sulfoxide / 36 h / 100 °C
3.1: pyridine; thionyl chloride / 0 °C
4.1: diethyl ether / 2 h / Reflux
4.2: 3 h / Reflux
5.1: sodium hydrogencarbonate / ethanol / 36 h / 20 °C
6.1: tetrahydrofuran / 10 - 15 °C
6.2: 0.33 h / 25 - 30 °C
7.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C
View Scheme

: 116673-94-0
4-chloro-3,3-dimethylbutyronitrile

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: diethyl ether / 2 h / Reflux 1.2: 3 h / Reflux 2.1: sodium hydrogencarbonate / ethanol / 36 h / 20 °C 3.1: tetrahydrofuran / 10 - 15 °C 3.2: 0.33 h / 25 - 30 °C 4.1: hydrazine hydrate; potassium hydroxide / ethylene diglycol / 7 h / 85 - 145 °C View Scheme
Multi-step reaction with 5 steps 1.1: magnesium 1.2: 5 h / Reflux 2.1: sodium hydrogencarbonate / ethanol; water / 36 h / 20 °C 3.1: tetrahydrofuran / 10 - 15 °C 4.1: water / tetrahydrofuran / 0.33 h / 25 - 30 °C 5.1: hydrazine hydrate; potassium hydroxide / diethylene glycol / 7 h / 85 - 145 °C View Scheme

: 1310936-45-8
C23H19Cl2NO2

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: water / tetrahydrofuran / 0.33 h / 25 - 30 °C 2: hydrazine hydrate; potassium hydroxide / diethylene glycol / 7 h / 85 - 145 °C View Scheme

: 100-44-7
benzyl chloride

: 156897-06-2
licofelone

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: magnesium 1.2: 5 h / Reflux 2.1: sodium hydrogencarbonate / ethanol; water / 36 h / 20 °C 3.1: tetrahydrofuran / 10 - 15 °C 4.1: water / tetrahydrofuran / 0.33 h / 25 - 30 °C 5.1: hydrazine hydrate; potassium hydroxide / diethylene glycol / 7 h / 85 - 145 °C View Scheme

: 6066-82-6
1-hydroxy-pyrrolidine-2,5-dione

: 156897-06-2
licofelone

: licofelone-NHS

Conditions

Conditions	Yield
With dicyclohexyl-carbodiimide In dichloromethane at 20℃;	100%
With dicyclohexyl-carbodiimide In dichloromethane at 20℃;

: 156897-06-2
licofelone

: 530-62-1
1,1'-carbonyldiimidazole

: 1175530-60-5
2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)-1-(1H-imidazol-1-yl)ethanone

Conditions

Conditions	Yield
In tetrahydrofuran at 20℃; for 24h;	97%
In tetrahydrofuran at 20℃; for 0.5h;

: 156897-06-2
licofelone

: 77-86-1
2-amino-2-hydroxymethyl-1,3-propanediol

: 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-ylacetic acid tromethamine salt

Conditions

Conditions	Yield
In ethanol at 47℃; Industry scale;	92%

: 123-41-1
cholin hydroxide

: 156897-06-2
licofelone

: 1224948-00-8
6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-ylacetic acid choline salt

Conditions

Conditions	Yield
In ethanol; water at 75 - 77℃; Product distribution / selectivity; Industry scale;	87%

: 2,2,2-trichloroethyl 2,3,4-tri-O-tert-butyldimethylsilyl-D-glucopyranuronate

: 156897-06-2
licofelone

: (2S,3R,4S,5R)-3,4,5-Tris-(tert-butyl-dimethyl-silanyloxy)-6-{2-[2-(4-chloro-phenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl]-acetoxy}-tetrahydro-pyran-2-carboxylic acid 2,2,2-trichloro-ethyl ester

Conditions

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -50 - 20℃; for 2h;	72%

: 24772-63-2
1,8-diiodooctane

: 156897-06-2
licofelone

: 1332505-35-7
8-iodooctyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate

Conditions

Conditions	Yield
With potassium carbonate In acetone at 56℃;	70.1%

: 108-88-3
toluene

: 156897-06-2
licofelone

: 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-ylacetic acid toluene hemisolvate

Conditions

Conditions	Yield
In diethyl ether at 60℃;	70%

: 109-64-8
1,3-dibromo-propane

: 156897-06-2
licofelone

: 1332505-34-6
3-bromopropyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate

Conditions

Conditions	Yield
With potassium carbonate In acetone at 56℃;	68.7%

: 106-93-4
ethylene dibromide

: 156897-06-2
licofelone

: 1025054-99-2
2-bromoethyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate

Conditions

Conditions	Yield
With potassium carbonate In acetone at 56℃;	60.3%

: 110-52-1
1,4-dibromo-butane

: 156897-06-2
licofelone

: 912341-47-0
4-bromobutyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate

Conditions

Conditions	Yield
With potassium carbonate In acetone at 56℃;	56.9%

: 3344-70-5
1,12-dibromododecane

: 156897-06-2
licofelone

: 1332505-36-8
12-bromododecyl 2-(6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl)acetate

Conditions

Conditions	Yield
With potassium carbonate In acetone at 56℃;	43.1%

: 156897-06-2
licofelone

: [2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl]acetic acid 2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl ester

Conditions

Conditions	Yield
With boron trifluoride diethyl etherate In diethyl ether at 20℃; for 0.5h;	1.3%

: 108-88-3
toluene

: 156897-06-2
licofelone

: 6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-ylacetic acid toluene solvate

Conditions

Conditions	Yield
In ethyl acetate at 40 - 50℃;

Licofelone Specification

The Licofelone is an organic compound with the formula C₂₃H₂₂ClNO₂. The systematic name of this chemical is [6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid. With the CAS registry number 156897-06-2, it is also named as (2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)acetic acid. The product's categories are Intermediates & Fine Chemicals; Pharmaceuticals. Besides, it is a dual COX/LOX inhibitor being considered as a treatment for osteoarthritis. Licofelone is both an analgesic and an anti-inflammatory. Inhibition of 5-LOX may reduce the gastrointestinal toxicity associated with other non-steroidal anti-inflammatory drugs, which only inhibit COX (cyclooxygenase).

Physical properties about Licofelone are: (1)ACD/LogP: 6.73; (2)# of Rule of 5 Violations: 1; (3)ACD/LogD (pH 5.5): 5.66; (4)ACD/LogD (pH 7.4): 3.86; (5)ACD/BCF (pH 5.5): 6567.38; (6)ACD/BCF (pH 7.4): 103.76; (7)ACD/KOC (pH 5.5): 9340.49; (8)ACD/KOC (pH 7.4): 147.58; (9)#H bond acceptors: 3; (10)#H bond donors: 1; (11)#Freely Rotating Bonds: 4; (12)Polar Surface Area: 31.23 Å²; (13)Index of Refraction: 1.626; (14)Molar Refractivity: 108.77 cm³; (15)Molar Volume: 306.9 cm³; (16)Polarizability: 43.12×10^-24cm³; (17)Surface Tension: 45.5 dyne/cm; (18)Density: 1.23 g/cm³; (19)Flash Point: 280.2 °C; (20)Enthalpy of Vaporization: 86.01 kJ/mol; (21)Boiling Point: 539.7 °C at 760 mmHg; (22)Vapour Pressure: 1.76E-12 mmHg at 25°C.

You can still convert the following datas into molecular structure:
(1)SMILES: Clc4ccc(c1c(n3c(c1c2ccccc2)CC(C)(C3)C)CC(=O)O)cc4
(2)InChI: InChI=1/C23H22ClNO2/c1-23(2)13-19-22(15-6-4-3-5-7-15)21(16-8-10-17(24)11-9-16)18(12-20(26)27)25(19)14-23/h3-11H,12-14H2,1-2H3,(H,26,27)
(3)InChIKey: UAWXGRJVZSAUSZ-UHFFFAOYAP
(4)Std. InChI: InChI=1S/C23H22ClNO2/c1-23(2)13-19-22(15-6-4-3-5-7-15)21(16-8-10-17(24)11-9-16)18(12-20(26)27)25(19)14-23/h3-11H,12-14H2,1-2H3,(H,26,27)
(5)Std. InChIKey: UAWXGRJVZSAUSZ-UHFFFAOYSA-N

The toxicity data is as follows:

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
mouse	LD	oral	> 300mg/kg (300mg/kg)		Arzneimittel-Forschung. Drug Research. Vol. 45, Pg. 159, 1995.

Product Name

Licofelone

Synthetic route

Licofelone Specification

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