Improvements in or relating to process for the manufacture of cyclopentanophenanthrene derivatives

摘要

2a -methyl - dihydrotestosterone, 17 - esters thereof and 2a -methyl-17a -lower alkyl-dihydrotestosterones in which the alkyl group contains at most six carbon atoms, are prepared by hydrogenating the corresponding 2-hydroxymethylene or 2-acyloxymethylene derivtives in the presence of a hydrogenation catalyst, e.g. platinum oxide or palladium. The 2-hydroxymethylene compounds are obtained by reacting the 2-unsubstituted dihydrotestosterone with ethyl formate and sodium hydride, followed by acid treatment, and if desired the hydroxy group (together with the 17b -hydroxyl if a secondary alcoholic group) may be acylated prior to hydrogenation. Specified acyl groups are those derived from hydrocarbon carboxylic acids of from 2 to 12 carbon atoms, especially the acetyl, propionyl and benzoyl groups. In examples:-(1) dihydrotestosterone in benzene is stirred with ethyl formate and sodium hydride under nitrogen, the resulting sodium salt acidified with HCl and the 2-hydroxymethylene dihydrotesterone produced hydrogenated in methanol over palladium-charcoal, treated with aqueous KOH, acidified and 2a -methyl dihydrotesterone isolated by solvent extraction and purified by chromatography on alumina; (2) as above, effecting the hydrogenation in acetic acid; (3) the intermediate 2-hydroxymethylene compound is acetylated prior to hydrogenation; (4) and (5), 17a -methyl- and 17a -ethyl dihydrotestosterone similarly yield 2a ,17a -dimethyl and 2a -methyl-17-ethyl-dihydrotestosterone respectively; (6) 2-hydroxymethylene-dihydrotestosterone is acylated with propionic anhydridepyridine and hydrogenated to the propionate of 2a -methyl-dihydrotestosterone. Specifications 853,291 and 854,407 are referred to.