Patent GB-1247641-A (GB)
Title: 9alpha-FLUORO-16-FLUOROMETHYLENEPREDNISOLONE-21-ESTER AND PREPARATION THEREOF
IPC: H01R4/02
Filed: 1970-01-20
Abstract: 1,247,641. 9α - Fluoro - -16 - fluoromethyleneprednisolone 21-enanthate. MERCK PATENT G.m.b.H. 20 Jan., 1970 |11 Feb., 1969], No. 2720/70. Heading C2U. The title compound is prepared by (a) esterifying or transesterifying the free 21-ol or a C 1-4  ester thereof with enanthic acid or a reactive derivative thereof; or (b) treating the corresponding 16α,17α-epoxy-16#-fluoromethyl compound with HC1 or HBr in an anhydrous solvent; or (c) chemically or microbiologically dehydrogenating the corresponding #<SP>4</SP> compound; or (d) reacting the corresponding 9#,11#- epoxide or 16#-fluoromethyl-9#,11#; 16α,17α- diepoxide with HF; or (c) reacting the corresponding 21-unsubstituted steroid with iodine in an alkaline solution and then reacting the product with a salt of enanthic acid; or (f) dehydrohalogenating the corresponding 2-halo- #<SP>4</SP>-compound or 2,4-dihalo-ring A-saturated compound 9α - Fluoro - 11#,21 - dihydroxy - 16α,17α- epoxy - 16# - fluormethyl - 1,4 - pregnadiene - 3,20 - dione 21 - enanthate is prepared by esterifying 9α - fluoro - 11#,17α,21 - trihydroxy - 16- methylene - 1,4 - pregnadiene - 3,20 - dione with enanthic acid chloride, reacting the 21-enanthate with N-bromosuccinimide to form the correspondiny 16#-bromomethyl 16α,17α-epoxide and reacting this with AgF in acetonitrile. 9α - Fluoro - 16 - fluoromethylenehydrocortisone 21 -enanthate is prepared by esterification of the 21-ol. 9#,11#; 16α,17α - Diepoxy - 16#- fluoromethyl - 21 - hydroxy - 1,4 - pregnadiene- 3,20-dione 21-enanthate is prepared by esterifying 9#,11#- epoxy - 16 - methylene - 17α,21- dihydroxy - 1,4 - pregnadiene - 3,20 - dione, reacting the 21-enanthate with N-bromosuccinimide to form the corresponding 16#8-romomethyl-16α,17α-epoxide, and reacting this with AgF in acetonitrile. 9α-Fluoro-11#,17α-dihydroxy - 16 - fluomethylene - 1,4 - pregnadiene- 3,20-dione is prepared by reacting 9α-fluoro- 11#,17α - dihydroxy - 16 - methylene - 1,4 - pregnadiene - 3,20 - dione with N - bromosuccinimide to form the corresponding 16#-bromomethyl- 16α,17α-epoxide, reacting this with AgF in acetonitrile to form the corresponding 16#-fluoromethyl - 16α,17α - epoxide and splitting this with aqueous acid. 9#,11#-Epoxy-16-fluoromethylene,- 17α,21 - dihydroxy - 1,4 - pregnadiene- 3,20-dione 21-enanthate is prepared by treating 16 - fluoromethyleneprednisolone 11 - tosylate with sodium acetate and acetic acid to give 16- fluoromethylene- 1,4,9(11) - pregnatriene 17α,21- diol-3,20-dione, adding HOBr to give the 9α- bromo-11#-ol, dehydrobrominating to give the 9#,11#-epoxide and esterifying this. 2-Bromo-9α- fluoro - 16 - fluoromethylenehydrocortisone 21- enanthate is prepared by bromination of the 2- unsubstituted compound; 2,4 - dibromo - 9α- fluoro - 11#,17α - dihydroxy 16 - fluoromethylene- 21 - enanthoyloxy - pregnane - 3,20 - dione is prepared similarly. The steroid of the invention is stated to be an antiproliterative agent and to be of use in treating skin diseases such as psoriasis, and it may be made up into pharmaceutical compositions with suitable carriers. Reference has been directed by the Comptroller to Specification 963,428.