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SYNTHESIS AND PURIFICATION OF FLUMETASONE PIVALATE [2-[(6S,9R,11S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11, 12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl]2,2-dimethylpropanoate

IP.com Disclosure Number: IPCOM000190208D
Publication Date: 2009-Nov-20
Document File: 2 page(s) / 96K

Publishing Venue

The IP.com Prior Art Database

Abstract

A process to obtain Flumetasone Pivalate [2-[(6S,9R,11S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl]2,2-dimethylpropanoate.

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       SYNTHESIS AND PURIFICATION OF FLUMETASONE PIVALATE [2-[(6S,9R,11S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11, 12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl]2,2-dimethylpropanoate

ABSTRACT

A process to obtain Flumetasone Pivalate [2-[(6S,9R,11S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-

trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl]2,2-dimethylpropanoate.

DESCRIPTION

A process for the synthesis of Flumetasone Pivalate [2-[(6S,9R,11S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-

10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl]2,2-

dimethylpropanoate is disclosed.

The reaction is carried out in one step, and the crude product is then purified by crystallizations in organic solvents.

REACTION PATHWAY

1st Step

O

O

CH3

O

H

C

H3

C

H3

OH

CH3

O

H

O

H

O

O

H

CH3

Dichloromethane Triethylamine 4-DMAP Pivaloil chloride

CH3

CH3

O

CH3

CH3

F

F

O

O

F

F

1

2

First purification of Crude Flumetasone Pivalate

O

H

O

O

H

CH3

C

 H3 C

H3

CH3

CH3

O

H

O

O

H

C

 H3 C

H3

CH3

O

O

CH3

CH3

O

O

C

H3

C

H3

Methanol

F

F

O

O

F

F

2

2

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Second purification of Flumetasone Pivalate 1st Purified

C

 H3 C

H3

CH3

O

O

O

H

O

H

O

H

CH3

O

O

H

CH3

C

 H3 C

H3

CH3

O

CH3

CH3

O

O

C

H3

C

H3

Acetone

Purified Water

F

F

O

O

F

F

2

2

EXAMPLES:

1st step: synthesis of Flumetasone Pivalate

In a reactor charge 4-Dimethylamino pyridine (4-DMAP), dichloromethane and triethylamine. The reaction mixture is cooled to 0 ÷ 5 °C and a solution of pivaloil chloride in dichloromet...