1879-77-2

Basic information

• Product Name: doxibetasol
• Synonyms: doxibetasol;9-Fluoro-11,17-dihydroxy-16-methylpregna-1,4-diene-3,20-dione;9-Fluoro-16-methylpregna-1,4-diene-11,17-diol-3,20-dione;16β-Methyl-11β,17-dihydroxy-9-fluoro-5α-pregnane-1,4-diene-3,20-dione;(8S,9R,10S,11S,13S,14S,16S,17R)-17-acetyl-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one;(8S,9R,10S,11S,13S,14S,16S,17R)-17-ethanoyl-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
• CAS NO: 1879-77-2
• Molecular Formula: C22H29FO4
• Molecular Weight: 376.465
• EINECS: 217-535-2
• Mol File: 1879-77-2.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 527.1°Cat760mmHg
• Flash Point: 272.6°C
• Appearance: /
• Density: 1.25g/cm³
• Vapor Pressure: 2.59E-13mmHg at 25°C
• Refractive Index: 1.574
• CAS DataBase Reference: doxibetasol(CAS DataBase Reference)
• NIST Chemistry Reference: doxibetasol(1879-77-2)
• EPA Substance Registry System: doxibetasol(1879-77-2)

Safety Data

• Hazardous Substances Data: 1879-77-2(Hazardous Substances Data)

Usage

Uses

Doxybetasol (Betamethasone Valerate EP Impurity B) is an impurity of Betamethasone (B327000), which is a glucocorticoid used as an anti-inflammatory agent.

InChI:InChI=1/C22H29FO4/c1-12-9-17-16-6-5-14-10-15(25)7-8-19(14,3)21(16,23)18(26)11-20(17,4)22(12,27)13(2)24/h7-8,10,12,16-18,26-27H,5-6,9,11H2,1-4H3/t12-,16-,17-,18-,19-,20-,21-,22-/m0/s1

Synthetic route

C22H28FIO4 → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions	Yield
With bismuth(III) oxide; N-ethyl-N,N-diisopropylamine; para-thiocresol In dichloromethane for 2h; Irradiation;	92%

16β-methyl-9β,11β-epoxy-17α-hydroxy-1,4-pregnadiene-3,20-dione (37413-99-3) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions	Yield
With hydrogen fluoride In tetrahydrofuran; dichloromethane at -70 - 0℃; for 5h;	80%

16α,17α-epoxy-3β-hydroxy-5α-pregn-9(11)-en-20-one (884488-47-5) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: 95 percent / pyridine / 20 °C 2.1: 70 percent / triethyl orthoformate; p-toluenesulfonic acid / CH2Cl2 / 20 h / 20 °C 3.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 4.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 4.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 5.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 5.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 6.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

16β-methyl-3β,17α-dihydroxy-20,20-ethylenedioxy-5α-pregn-9(11)-ene (884488-49-7) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 3 steps 1.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 1.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 2.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 2.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 3.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

3β-acetoxy-16α,17α-epoxy-20,20-ethylenedioxy-5α-pregn-9(11)-ene (884488-48-6) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 2.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 2.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 3.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 3.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 4.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

16β-methyl-17α-hydroxy-pregna-1,4,9(11)-triene-3,20-dione (14135-32-1) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 1.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 2.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

20-oxo-5α-pregna-9(11),16-dien-3β-yl acetate (21650-83-9) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: 91.7 percent / hydrogen peroxide; sodium hydroxide / methanol / 2 h / 20 °C 2.1: 95 percent / pyridine / 20 °C 3.1: 70 percent / triethyl orthoformate; p-toluenesulfonic acid / CH2Cl2 / 20 h / 20 °C 4.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 5.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 5.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 6.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 6.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 7.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

Δ9(11)22-isoallospirosten-3β-ol (1106-20-3) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: pyridine; ammonium chloride / 125 - 135 °C 1.2: acetic acid; chromium trioxide / H2O; 1,2-dichloro-ethane / 1 h / 20 °C 1.3: 57 percent / aluminium oxide / benzene / 2 h 2.1: 91.7 percent / hydrogen peroxide; sodium hydroxide / methanol / 2 h / 20 °C 3.1: 95 percent / pyridine / 20 °C 4.1: 70 percent / triethyl orthoformate; p-toluenesulfonic acid / CH2Cl2 / 20 h / 20 °C 5.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 6.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 6.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 7.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 7.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 8.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

3β-acetoxy-16α,17α-epoxy-5α-pregn-9(11)-en-20-one (113926-56-0) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 70 percent / triethyl orthoformate; p-toluenesulfonic acid / CH2Cl2 / 20 h / 20 °C 2.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 3.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 3.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 4.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 4.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 5.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

Δ9(11)22-isoallospirosten-3β-ol-12-one-3-acetate (989-73-1) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: hydrazine hydrate / ethane-1,2-diol / 1 h / Heating 1.2: 95 percent / potassium hydroxide / ethane-1,2-diol; H2O / 5 h / 195 - 197 °C 2.1: pyridine; ammonium chloride / 125 - 135 °C 2.2: acetic acid; chromium trioxide / H2O; 1,2-dichloro-ethane / 1 h / 20 °C 2.3: 57 percent / aluminium oxide / benzene / 2 h 3.1: 91.7 percent / hydrogen peroxide; sodium hydroxide / methanol / 2 h / 20 °C 4.1: 95 percent / pyridine / 20 °C 5.1: 70 percent / triethyl orthoformate; p-toluenesulfonic acid / CH2Cl2 / 20 h / 20 °C 6.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 7.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 7.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 8.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 8.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 9.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

hecogenin (467-55-0) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: 95 percent / pyridine / 20 °C 2.1: 72 percent / m-iodoxybenzoic acid; diphenyl diselenide / toluene / 12 h / Heating 3.1: hydrazine hydrate / ethane-1,2-diol / 1 h / Heating 3.2: 95 percent / potassium hydroxide / ethane-1,2-diol; H2O / 5 h / 195 - 197 °C 4.1: pyridine; ammonium chloride / 125 - 135 °C 4.2: acetic acid; chromium trioxide / H2O; 1,2-dichloro-ethane / 1 h / 20 °C 4.3: 57 percent / aluminium oxide / benzene / 2 h 5.1: 91.7 percent / hydrogen peroxide; sodium hydroxide / methanol / 2 h / 20 °C 6.1: 95 percent / pyridine / 20 °C 7.1: 70 percent / triethyl orthoformate; p-toluenesulfonic acid / CH2Cl2 / 20 h / 20 °C 8.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 9.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 9.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 10.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 10.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 11.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

hecogenin acetate (915-35-5) → 16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2)

Conditions

Yield

Multi-step reaction with 10 steps 1.1: 72 percent / m-iodoxybenzoic acid; diphenyl diselenide / toluene / 12 h / Heating 2.1: hydrazine hydrate / ethane-1,2-diol / 1 h / Heating 2.2: 95 percent / potassium hydroxide / ethane-1,2-diol; H2O / 5 h / 195 - 197 °C 3.1: pyridine; ammonium chloride / 125 - 135 °C 3.2: acetic acid; chromium trioxide / H2O; 1,2-dichloro-ethane / 1 h / 20 °C 3.3: 57 percent / aluminium oxide / benzene / 2 h 4.1: 91.7 percent / hydrogen peroxide; sodium hydroxide / methanol / 2 h / 20 °C 5.1: 95 percent / pyridine / 20 °C 6.1: 70 percent / triethyl orthoformate; p-toluenesulfonic acid / CH2Cl2 / 20 h / 20 °C 7.1: 72 percent / tetrahydrofuran; diethyl ether / 72 h / 60 °C 8.1: m-iodoxybenzoic acid; diphenyl diselenide / toluene / 22 h / Heating 8.2: 50 percent / p-toluenesulfonic acid / CH2Cl2 / 4 h / 20 °C 9.1: perchloric acid; 1,3-dibromo-5,5-dimethylhydantoin / dimethylformamide / 3 h / cooling 9.2: 75.8 percent / sodium hydroxide / CH2Cl2; methanol; H2O / 2 h / cooling 10.1: 80 percent / hydrofluoric acid / tetrahydrofuran; CH2Cl2 / 5 h / -70 - 0 °C View Scheme

16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2) → (8S,9R,10S,11S,13S,14S,16S,17R)-17-(2,2-Diiodo-acetyl)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-one (37414-01-0)

Conditions	Yield
With iodine; calcium chloride; calcium oxide In methanol at 25 - 27℃; for 1h;	100%

16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2) → betamethasone (378-44-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 100 percent / anhydrous calcium chloride; calcium oxide; iodine / methanol / 1 h / 25 - 27 °C 2: 180 mg / acetic acid / acetone; H2O / 3 h / Heating 3: 90 percent / sodium methoxide; methanol / 4 h / 25 °C View Scheme

16β-methyl-9α-fluoro-11β,17α-dihydroxy-1,4-pregnadiene-3,20-dione (1879-77-2) → betamethasone 21-acetate (987-24-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / anhydrous calcium chloride; calcium oxide; iodine / methanol / 1 h / 25 - 27 °C 2: 180 mg / acetic acid / acetone; H2O / 3 h / Heating View Scheme

Upstream product

• 14135-32-1 16β-methyl-17α-hydroxy-pregna-1,4,9(11)-triene-3,20-dione 
• 884488-48-6 3β-acetoxy-16α,17α-epoxy-20,20-ethylenedioxy-5α-pregn-9(11)-ene 
• 884488-49-7 16β-methyl-3β,17α-dihydroxy-20,20-ethylenedioxy-5α-pregn-9(11)-ene 
• 884488-47-5 16α,17α-epoxy-3β-hydroxy-5α-pregn-9(11)-en-20-one 
• 37413-99-3 16β-methyl-9β,11β-epoxy-17α-hydroxy-1,4-pregnadiene-3,20-dione 
• 915-35-5 hecogenin acetate 
• 467-55-0 hecogenin 
• 989-73-1 Δ⁹⁽¹¹⁾22-isoallospirosten-3β-ol-12-one-3-acetate 
• 113926-56-0 3β-acetoxy-16α,17α-epoxy-5α-pregn-9(11)-en-20-one 
• 1106-20-3 Δ⁹⁽¹¹⁾22-isoallospirosten-3β-ol 
• 21650-83-9 20-oxo-5α-pregna-9(11),16-dien-3β-yl acetate 

Downstream Products

• 987-24-6 betamethasone 21-acetate 
• 378-44-9 betamethasone 
• 37414-01-0 (8S,9R,10S,11S,13S,14S,16S,17R)-17-(2,2-Diiodo-acetyl)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-one 

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