Manufacture of new esters of 20:21-ketols of the pregnene series

摘要

The invention comprises 21-esters of furane-2-carboxylic acid and D 4-3-keto- and D 5-3-hydroxy-20-keto-21-hydroxy-pregnenes which may contain a hydroxy group in the 17-position and/or a hydroxy or a keto group in the 11-position and the preparation thereof by the methods described in the examples. In the examples desoxycorticosterone - furate - (2) is prepared by treating desoxycorticosterone with furane-2-carboxylic acid chloride in the presence of pyridine while cooling and by refluxing D 4-3,20-diketo-21-chloropregnene and the sodium salt of furane-2-carboxylic acid in acetone, D 5 - 20 - keto - 3b ,21 - dihydroxy - pregnene-21-furoate-(2) is prepared by heating D 5 - 3b - hydroxy - 20 - keto - 21 - diazo - pregnene with furane-2-carboxylic acid in xylene and may be oxidized to desoxycorticosterone-furoate-(2) with cyclohexanone and aluminium isopropylate, D 4 - 3,11,20 - triketo - 17a - hydroxy - 21 - furoyl - (2) - oxypregnene is prepared by treating D 4-3,11,20-triketo-17a , 21-dihydroxy-pregnene with furane-2-carboxylic acid chloride in pyridine while cooling, and D 4 - 3,20 - diketo - 17a - hydroxy - 21 - furoyl - (2)-oxypregnene is similarly prepared using the acid chloride. Other reactants mentioned are D 5 - 20 - keto - 3,21 - dihydroxy - pregnene, D 4-3,20 - diketo - 11,21 - dihydroxy - pregnene and D 4 - 3,20 - diketo - 11,17a ,21 - trihydroxy - pregnene. Other esterification methods mentioned are those using esters, halides or the anhydride of furane-2-carboxylic acid with the required 20,21-ketols in the presence or absence of condensing agents, or furane-2-carboxylic acid or its salts may be reacted with esters of the required 20,21-ketols especially those with hydrohalic acids.