Patent GB-1352079-A (GB)
Title: Process for preparing steroid ketals
IPC: C07C/
Filed: 1972-01-05
Abstract: 1352079 6-Substituted steroids E I DU PONT DE NEMOURS & CO 5 Jan 1972 [11 Jan 1971] 471/72 Heading C2U The invention comprises (A) the products of steps (a), (b) and (c) in the Reaction Scheme infra (wherein R<SP>1</SP> and R<SP>4</SP> are each C 1-5  alkyl, and R<SP>2</SP> and R<SP>3</SP> are each C 1-6  alkyl, C 5-6  cycloalkyl or phenyl, or R<SP>2</SP> and R<SP>3</SP> together form tetra- or penta-methylene); (B) the products of steps (d) and (e) wherein R<SP>2</SP> = R<SP>3</SP> = Me; and (C) 5α,6,6- trifluoro - 16α,17α - isopropylidenedioxy - 21- acetoxypregnane-3,20-dione which is obtainable by oxidizing the product of step (e). Specified reactants are: step (a) -NOF or NOF/NOBF 4 ; step (b) -neutral alumina; step (c) -SF 4 /HF, SF 4 /BF 3  or SF 4 /SbF 5 , the SF 4  being replaceable by SeF 4  or PhSF 3 ; step (d) -aqueous alkali; step (e) Ac 2 O/py. 3#,21 - Diacetoxy - 16α,17α - isopropylidenedioxypregn-5-en-20-one is prepared by acetylation of the corresponding 3,21-diol. 6,6,9α-Trifluoro - 11# - hydroxy - 16α, 17α- isopropylidenedioxy - 21 - chloropregna - 1,4- diene-3,20-dione (XXII) is prepared from compound C above by the sequence: C#6,6-difluoro - 16α,17α - isopropylidenedioxy - 21- acetovypregn - 4 - ene - 3,20 - dione (X) # 6,6- difluoro - 16α,17α - isopropylidenedioxy - 21- hydroxypregn - 4 - ene - 3,20 - dione (XI) # 6, 6 - difluoro - 11#,21 - dihydroxy - 16α,17α - isopropylidenedioxypregn - 4 - ene - 3,20 - dione (XIII) # 6,6 - difluoro - 11# - hydroxy- 16α,17α - isopropylidenedioxy - 21 - acetoxypregn- 4 - ene - 3,20 - dione (XII) # 6,6-difluoro- 16α,17α - isopropylidenedioxy - 21 - acetoxypregna - 4,9(11) - diene - 3,20 - dione (XVI) # 6,6- difluoro - 9α - bromo - 11# - hydroxy - 16α,17α- isopropylidenedioxy - 21 - acetoxypregn - 4 - ene- 3,20 - dione (XVII) # 6,6 - difluoro - 9#,11#- epoxy - 16α,17α - isopropylidenedioxy - 21- acetoxypregn - 4 - ene - 3,20 - dione (XVIII) # 6,6,9α - trifluoro - 11# - hydroxy - 16α,17α- isopropylidenedioxy - 21 - acetoxypregn - 4 - ene- 3,20 - dione (XIX) # 6,6,9α - trifluoro - 11#- hydroxy - 16α,17α - isopropylidenedioxy - 21- acetoxypregna - 1,4 - diene - 3,20 - dione (XX) # 6,6,9α - trifluoro - 11#,21 - dihydroxy - 16α, 17α - isopropylidenedioxypregna - 1,4 - diene- 3,20 - dione (XXI) # 6,6,9α - trifluoro - 11#- hydroxy - 16α,17α - isopropylidenedioxy - 21- mesyloxypregna - 1,4 - diene - 3,20 - dione # XXII. Compound XII above is also obtainable from X by direct microbial hydroxylation. 6,6 - Difluoro - 11# - hydroxy - 16α,17α - isopropylidenedioxy - 21 - acetoxypregna - 1,4 - diene- 3,20--dione (XXIII) is prepared from XII with DDQ. 6,6 - Difluoro - 11# - hydroxy - 16α,17α - isopropylidenedioxy - 21 - chloro - pregna - 1,4- diene-3,20-dione (XV) is prepared from XIII by the sequence: XIII # 6,6-difluoro-11#,21- dihydroxy - 16α,17α - isopropylidenedioxypregna. 1,4 - diene - 3,20 - dione (XIV) # 6,6-difluoro- 11# - hydroxy - 21 - mesyloxy - 16α,17α - isopropylidenedioxypregna-1,4-diene-3,20-dione# XV. 6,6 - Difluoro - 11# - hydroxy - 16α,17α - isopropylidenedioxy - 21 - chloropregn - 4 - ene-3,20- dione (XXIV) is prepared from XIII via the 21- mesylate thereof. General reference is also made to the 11-oxo analogues of compounds XII, XIII, XIV and XXIII. The inventive compounds and also compounds X-XV, XIX-XX, XXII-XXIV and the 11- oxo analogues of compounds XII, XIII, XIV and XXIII are said to possess antiinflammatory, glucocorticoid, progestational, antiestrogenic and antiandrogenic activities, and may be made up with carriers into pharmaceutical compositions for oral, parenteral and topical administration.