CONVENIENT SYNTHESIS OF S-FLUOROMETHYL 6ALPHA, 9ALPHA-DIFLUORO-11BETA-HYDROXY-16ALPHA- METHYL-17ALPHA-PROPIONYLOXY-3-OXOANDROSTA-1, 4-DIENE-17BETA-CARBOTHIOATE

摘要

The present invention provides a convenient process for the preparation of S-fluoromethyl 6a, 9a-difluoro-11b-hydroxy-16a-methyl-17a-propionyloxy-3-oxoandrosta-1, 4-diene-17b-carbothioate, a compound of formula 1, comprising(a) treating 17b-[(N, N-dimethylcarbamoyl)thio]carbonyl-6a,9a-difluoro-11b-hydroxy-16a-methyl-17a-propionyloxy-3-oxoandrosta-1, 4-diene, a compound of formula 3 with alkali metal carbonate-alcohol system to obtain 6a, 9a-difluoro-11b-hydroxy-16a-methyl-17a-propionyloxy-3-oxoandrosta-1, 4-diene-17b-carbothioic acid, a compound of formula 4; (b) reacting the compound of formula 4 with bromofluoromethane to yield the compound of formula 1.The present invention also provides an improved process for preparation of compound of formula 1 comprising (a) reacting 6a, 9a-difluoro-11b-hydroxy-16a-methyl-3-oxo-17a-(propionyloxy) androsta-1, 4-dien-17b-carboxylic acid, a compound of formula 2, with N,N-dimethylthiocarbamoyl chloride in an inert aprotic solvent in the presence of an iodide catalyst and a base to give a compound of formula 3, (b) reacting the compound of formula 3 with a hydrosulfide reagent and bromofluromethane to obtain a compound of formula 1.