Patent GB-1330563-A (GB)
Title: 9beta, 10alpha-steroids their preparation and compositions containing the same
IPC: A61K9/00
Filed: 1971-04-19
Abstract: 1330563 1#,2# - Methylene - 9#,10α - steroids PHILIPS GLOEILAMPENFABRIEKEN NV 19 April 1971 [4 March 1970] 22847/71 Heading C2U [Also in Division A5] The invention comprises compounds of formula wherein X is H and Y is free or esterified hydroxy, or X+Y is oxo; R 3  is a 3-oxo-#<SP>4</SP>, 3- oxo-#<SP>4,6</SP>, 3-OR<SP>1</SP>-#<SP>3,5</SP>, 3α-OR<SP>1</SP>-#<SP>4,6</SP> or 3#-OR<SP>1</SP>- #<SP>4,6</SP> system (where OR<SP>1</SP> is an esterified or etherified hydroxy group); R 6  is H, Cl, F, Me, 6,6-difluoro or 6,6-dichloro with the proviso that when R 6  is H then R 7  is 6#,7#-methylene; R 7  is a 7-hydrogen atom or a 6#,7#-methylene group with the proviso that when R 7  is a 6#,7#- methylene group then R 6  is H, F or Cl and R 3  is a 3-oxo-#<SP>4</SP> system; R 13  is Me or Et; R 17  is C 1-5  etherified hydroxy or C 1-8  esterified hydroxy; and R 21  is H, F or free or esterified hydroxy. Compounds I are prepared (i) by esterifying or etherifying the corresponding 17α-(free hydroxy) compounds (wherein R 3  is 3-oxo-#<SP>4</SP> or 3-oxo-#<SP>4,6</SP>); (ii) by esterifying or etherifying the corresponding 3-(free hydroxy)-#<SP>4,6</SP> compounds; (iii) by halogenating the corresponding #<SP>3,5</SP>-3- OR<SP>1</SP>-6-unsubstituted compounds to give #<SP>4</SP>-3- oxo-6-(fluoro or chloro) compounds; (iv) by converting the corresponding 21-iodo compounds (wherein R 3  is 3-oxo-#<SP>4</SP>) either into 21- fluoro compounds using AgF preferably in the presence of CaF 2 , or into 21-acetoxy compounds using triethylaminoacetic acid and an alkali metal acetate; (v) by catalytic hydrogenation of the corresponding 6-methylene, 6-dichloromethylene or 6-dibromomethylene compounds (wherein R 3  is 3-oxo-#<SP>4</SP>) into 6-methyl compounds ; (vi) by isomerization of the corresponding #<SP>4</SP>-3-oxo-6-methylene compounds into #<SP>4,6</SP>- 3-oxo-6-methyl compounds under palladium catalysis; and (vii) by dehydration of the corresponding #<SP>4</SP>-3-oxo-6-halo-7-hydroxy compounds into #<SP>4,6</SP>-3-oxo-6-halo compounds. Compounds I are interconverted by (i) 20/21- esterification/de-esterification; (ii) 3-enol esterification/enol etherification; (iii) reduction of 20-oxo to hydroxy; (iv) 6,7-hydrogenation/ dehydrogenation; (v) 6-dihalogenation; and (vi) 6,7-methylenation. 1#,2# - Methylene - 6# - chloro - 7# - hydroxy- 17α - acetoxy - 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from 1#,2# - methylene - 17α - acetoxy - 9#,10α - pregna - 4,6 - diene - 3,20 - dione by reaction with chromyl chloride. 1#,2#; 6#,7# - Bismethylene - 6α - chloro - 17α- hydroxy - 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from 1#,2#-methylene-6-chloro-17α- acetoxy - 9#,10α - pregna - 4,6 - diene - 3,20- dione via 1#,2# - methylene - 6 - chloro - 17α- hydroxy - 9#,10α - pregna - 4,6 - diene - 3,20- dione. 1#,2# - Methylene - 6 - methyl - 17α -hydroxy - 9#, 10α - pregna - 4,6 - diene - 3,20 - dione (1V) is prepared from 17α - hydroxy - 9#,10α - pregna: 1,4,6,triene-3,20-dione (I) by the sequence, I -# 1#,2# - methylene - 17α - hydroxy - 9#- 10α - pregna - 4,6 - diene - 3,20 - dione (II) -# 1#,2# - methylene - 17α - hydroxy - 9#,10α - pregn- 4 - ene - 3,20 - dione (III) -# 1#,2# - methylene- 6# - trichloromethyl - 17α - hydroxy - 9#,10α- pregn-4-ene - 3,20 - dione -# 1#,2#; 6 - bismethylene - 17α - hydroxy - 9#,10α - pregn - 4 - ene- 3,20-dione -# IV. 1#,2#; 6#,7# - Bismethylene - 17α - hydroxy- 9#,10α - pregn - 4 - ene - 3,20 - dione is prepared from II by reaction with dimethylsulphoxonium methylide. 1#,2# - Methylene - 3,17α - diacetoxy - 9#,10α- pregna-3,5-dien-20-one is prepared from III by reaction with Ac 2 O. 1#,2# - Methylene - 6 - fluoro - 17α - hydroxy- 9#,10α - pregna - 4,6 - diene - 3,20 - dione is prepared by hydrolysis of the 17-acetate thereof. 1#,2# - Methylene - 3α - hydroxy - 6 - chloro- 17α - acetoxy - 9#,10α - pregna - 4,6 - dien - 20- one is prepared by NaBH 4  reduction of the corresponding 3,20-dione.