52-70-0

Basic information

• Product Name: 6alpha,9-difluoro-11beta,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate
• Synonyms: 6alpha,9-difluoro-11beta,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate;21-(Acetyloxy)-6α,9-difluoro-11β,17-dihydroxypregna-1,4-diene-3,20-dione;Einecs 200-150-9;Pregna-1,4-diene-3,20-dione, 21-(acetyloxy)-6,9-difluoro-11,17-dihydroxy-, (6alpha,11beta)-;Pregna-1,4-diene-3,20-dione, 6alpha,9-difluoro-11beta,17,21-trihydroxy-, 21-acetate;6α,9α-Difluoroprednisolone 21-Acetate;(6α,11β)-21-(Acetyloxy)-6,9-difluoro-11,17-dihydroxypregna-1,4-diene-3,20-dione
• CAS NO: 52-70-0
• Molecular Formula: C₂₃H₂₈F₂O₆
• Molecular Weight: 438.4616264
• EINECS: 200-150-9
• Product Categories: Pharmaceuticals, Intermediates & Fine Chemicals, Steroids
• Mol File: 52-70-0.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 578.1°Cat760mmHg
• Flash Point: 303.4°C
• Appearance: /
• Density: 1.35g/cm³
• Vapor Pressure: 8.98E-16mmHg at 25°C
• Refractive Index: 1.566
• Storage Temp.: Refrigerator
• Solubility: Acetone (Slightly), DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 6alpha,9-difluoro-11beta,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: 6alpha,9-difluoro-11beta,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate(52-70-0)
• EPA Substance Registry System: 6alpha,9-difluoro-11beta,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate(52-70-0)

Safety Data

• Hazardous Substances Data: 52-70-0(Hazardous Substances Data)

Usage

Uses

6α,9α-?Difluoroprednisolone 21-Acetate, is an impurity of Difluprednate (D445925), which is shown to have antiinflammatory activity.

InChI:InChI=1/C23H28F2O6/c1-12(26)31-11-19(29)22(30)7-5-14-15-9-17(24)16-8-13(27)4-6-20(16,2)23(15,25)18(28)10-21(14,22)3/h4,6,8,14-15,17-18,28,30H,5,7,9-11H2,1-3H3/t14-,15-,17-,18-,20-,21-,22-,23-/m0/s1

Synthetic route

21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (2964-95-6) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
With selenium(IV) oxide

21-acetoxy-9,11β-epoxy-6α-fluoro-17-hydroxy-9β-pregna-1,4-diene-3,20-dione (3802-45-7) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
With hydrogen fluoride

17α,21-diacetoxy-5α,6-oxide-3,3-ethylenedioxypregnan-20-one (106545-20-4) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions

Yield

Multi-step reaction with 9 steps 1: boron fluoride; diethyl ether; benzene 2: toluene-4-sulfonic acid 3: HCl; acetic acid 4: methanol.KOH 5: durch Inkubation mit Rinder-Nebennieren-Suspension und anschliessender Acetylierung 6: methanesulfonyl chloride; pyridine; DMF 7: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 8: HF / dann mit Acetanhydrid 9: SeO2 View Scheme

17,21-diacetoxy-4-pregnene-3,20-dione (1807-15-4) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions

Yield

Multi-step reaction with 11 steps 1: toluene-4-sulfonic acid / Entfernen des entstehenden Butanons 2: chloroform; monoperoxyphthalic acid; diethyl ether 3: boron fluoride; diethyl ether; benzene 4: toluene-4-sulfonic acid 5: HCl; acetic acid 6: methanol.KOH 7: durch Inkubation mit Rinder-Nebennieren-Suspension und anschliessender Acetylierung 8: methanesulfonyl chloride; pyridine; DMF 9: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 10: HF / dann mit Acetanhydrid 11: SeO2 View Scheme

pregna-4,9(11)-diene-6α-fluoro-3,20-dione-17-hydroxy-21-acetate (570-41-2) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 2: HF / dann mit Acetanhydrid 3: SeO2 View Scheme

5α-hydroxy-17α,21-diacetoxy-6β-fluoropregnane-3,20-dione (2967-03-5) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 7 steps 1: HCl; acetic acid 2: methanol.KOH 3: durch Inkubation mit Rinder-Nebennieren-Suspension und anschliessender Acetylierung 4: methanesulfonyl chloride; pyridine; DMF 5: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 6: HF / dann mit Acetanhydrid 7: SeO2 View Scheme

6α-fluoro-17,21-dihydroxy-pregn-4-ene-3,20-dione (3827-45-0) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: durch Inkubation mit Rinder-Nebennieren-Suspension und anschliessender Acetylierung 2: methanesulfonyl chloride; pyridine; DMF 3: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 4: HF / dann mit Acetanhydrid 5: SeO2 View Scheme

21-acetoxy-6α-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (1058-55-5) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: methanesulfonyl chloride; pyridine; DMF 2: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 3: HF / dann mit Acetanhydrid 4: SeO2 View Scheme

17,21-diacetoxy-6α-fluoro-pregn-4-ene-3,20-dione (3793-12-2) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: methanol.KOH 2: durch Inkubation mit Rinder-Nebennieren-Suspension und anschliessender Acetylierung 3: methanesulfonyl chloride; pyridine; DMF 4: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 5: HF / dann mit Acetanhydrid 6: SeO2 View Scheme

21-acetoxy-9,11β-epoxy-6α-fluoro-17-hydroxy-9β-pregn-4-ene-3,20-dione (3800-29-1, 7793-44-4) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: HF / dann mit Acetanhydrid 2: SeO2 View Scheme

17α,21-diacetoxy-3,3-ethylenedioxypregn-5-ene-20-one (145013-90-7) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions

Yield

Multi-step reaction with 10 steps 1: chloroform; monoperoxyphthalic acid; diethyl ether 2: boron fluoride; diethyl ether; benzene 3: toluene-4-sulfonic acid 4: HCl; acetic acid 5: methanol.KOH 6: durch Inkubation mit Rinder-Nebennieren-Suspension und anschliessender Acetylierung 7: methanesulfonyl chloride; pyridine; DMF 8: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 9: HF / dann mit Acetanhydrid 10: SeO2 View Scheme

17,21-diacetoxy-3,3-ethanediyldioxy-6β-fluoro-5-hydroxy-5α-pregnan-20-one (3793-37-1) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions

Yield

Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid 2: HCl; acetic acid 3: methanol.KOH 4: durch Inkubation mit Rinder-Nebennieren-Suspension und anschliessender Acetylierung 5: methanesulfonyl chloride; pyridine; DMF 6: N-bromo-acetamide; dioxane; aqueous perchloric acid / Erwaermen einer Loesung des Reaktionsprodukts in Aceton mit Kaliumacetat 7: HF / dann mit Acetanhydrid 8: SeO2 View Scheme

pregna-1,4,9(11)-triene-17α,21-diol-3,20-dione 21-acetate (4380-55-6) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: tetrafluoroboric acid; 5,5-dibromohydantoin / acetone; water / 0 - 5 °C 2: potassium carbonate / acetone; water / 16 h / 25 - 40 °C 3: pyridine / acetonitrile / 4 h / 82 - 84 °C / Inert atmosphere 4: Selectfluor / acetonitrile / -20 - -12 °C 5: hydrogen fluoride; tert-butylhydroquinone / dichloromethane / 2 h / -10 - -5 °C View Scheme

21-acetoxy-9-bromo-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (4224-31-1) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium carbonate / acetone; water / 16 h / 25 - 40 °C 2: pyridine / acetonitrile / 4 h / 82 - 84 °C / Inert atmosphere 3: Selectfluor / acetonitrile / -20 - -12 °C 4: hydrogen fluoride; tert-butylhydroquinone / dichloromethane / 2 h / -10 - -5 °C View Scheme

21-acetyloxy-9β,11β-epoxy-17α-hydroxy-1,4-diene-3,20-dione (38680-83-0) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / acetonitrile / 4 h / 82 - 84 °C / Inert atmosphere 2: Selectfluor / acetonitrile / -20 - -12 °C 3: hydrogen fluoride; tert-butylhydroquinone / dichloromethane / 2 h / -10 - -5 °C View Scheme

C30H32O7 → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Selectfluor / acetonitrile / -20 - -12 °C 2: hydrogen fluoride; tert-butylhydroquinone / dichloromethane / 2 h / -10 - -5 °C View Scheme

21-acetyloxy-9β,11β-epoxy-6α-fluoro-17α-hydroxy-1,4-diene-3,20-dione (3802-45-7) → 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0)

Conditions	Yield
With hydrogen fluoride; tert-butylhydroquinone In dichloromethane at -10 - -5℃; for 2h; Solvent; Reagent/catalyst;	637.5 g

21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0) → 6α,9α-fluprednisolone

Conditions	Yield
With water; sodium hydroxide In methanol; dichloromethane at 0 - 5℃; for 2.5h;	83.17%

21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione (52-70-0) → 6α,9-difluoro-11β,17,21-trihydroxy-pregna-1,4-diene-3,20-dione (806-29-1)

Conditions	Yield
With potassium hydrogencarbonate

Upstream product

• 106545-20-4 17α,21-diacetoxy-5α,6-oxide-3,3-ethylenedioxypregnan-20-one 
• 3802-45-7 21-acetyloxy-9β,11β-epoxy-6α-fluoro-17α-hydroxy-1,4-diene-3,20-dione 
• 38680-83-0 21-acetyloxy-9β,11β-epoxy-17α-hydroxy-1,4-diene-3,20-dione 
• 4224-31-1 21-acetoxy-9-bromo-11β,17-dihydroxy-pregna-1,4-diene-3,20-dione 
• 4380-55-6 pregna-1,4,9(11)-triene-17α,21-diol-3,20-dione 21-acetate 
• 3800-29-1 21-acetoxy-9,11β-epoxy-6α-fluoro-17-hydroxy-9β-pregn-4-ene-3,20-dione 
• 1807-15-4 17,21-diacetoxy-4-pregnene-3,20-dione 
• 3802-45-7 21-acetoxy-9,11β-epoxy-6α-fluoro-17-hydroxy-9β-pregna-1,4-diene-3,20-dione 
• 2964-95-6 21-acetoxy-6α,9-difluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione 
• 3793-37-1 17,21-diacetoxy-3,3-ethanediyldioxy-6β-fluoro-5-hydroxy-5α-pregnan-20-one 
• 145013-90-7 17α,21-diacetoxy-3,3-ethylenedioxypregn-5-ene-20-one 
• 3793-12-2 17,21-diacetoxy-6α-fluoro-pregn-4-ene-3,20-dione 
• 1058-55-5 21-acetoxy-6α-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione 
• 3827-45-0 6α-fluoro-17,21-dihydroxy-pregn-4-ene-3,20-dione 

Downstream Products

• 806-29-1 6α,9-difluoro-11β,17,21-trihydroxy-pregna-1,4-diene-3,20-dione 

Relevant articles and documents

Preparation method of 6alpha, 9alpha-difluoroprednisolone

The invention belongs to the technical field of steroid hormone preparation, and particularly relates to a preparation method of 6alpha, 9alpha-difluoroprednisolone. Anecortave dehydroacetate used asa starting raw material undergoes bromo-hydroxy epoxidation, 6-positon fluoridation, 9-position fluoridation and hydrolysis to prepare the 6alpha, 9alpha-difluoroprednisolone. The method taking the anecortave dehydroacetate as the starting raw material has the advantages of low prices, few isomers, few impurities and short reaction route.