GB845441A - Process for the ethinylation of 17-keto-steroids - Google Patents

Abstract

17-Hydroxy-17-ethinyl-steroids are prepared by reacting a 17-keto-steroid containing in the molecule a further unprotected keto group in the 3-position in continuous conjunction with at least one carbon-carbon double bond in the nucleus with an ethinylation reagent. Continuous conjugation excludes parallel conjugation such as exists when double bonds are present both in the 1, 2- and in the 4, 5-positions of the nucleus. The ethinylation may be carried out by means of acetylene and on alkali metal in liquid ammonia at a temperature below -40 DEG C. using more than 2 mols of alkali metal per mol of steroid, or by means of acetylene and an alkali metal achoholate of a tertiary alcohol-preferably more than 2 mols of alcoholate per mol of steroid. Suitable starting compounds are 3, 17-androstendiones and 19-nor-3, 17-androstendiones with at least one double bond in the 4, 5-or 1, 2 position and any other double bond in continuous conjugation. The starting compounds may contain further substituents, for example, in the 11-position, especially free or esterified hydroxy group. In the case where the unprotected 3-keto group is in continuous conjugation with a double bond in the 4(5)-position, the reaction may be carried out in the presence of acetone preferably in a quantity of more than 2 mols per mol of 17-ketosteroid reactant. In the examples 17-ethinyl-testosterone is prepared from androst-4-en-3, 17-dione, 19-nor-17-ethinyl-androst-4-en-17-ol-3-one is prepared from 19-nor-androst-4-en-3, 17-dione, and 17-ethinyl-D 6-dehydrotestosterone is prepared from D 4, 6-androstadien -3, 17-dione.