Verfahren zur Herstellung von 6-Methyl-17a-oxyprogesteron-17-acylaten

The invention comprises compounds of the formulae: wherein R1 is a lower alkyl radical containing from 1-4 carbon atoms, R11 is hydrogen or the acyl radical of a hydrocarbon carboxylic acid containing from 1-12 carbon atoms inclusive, and R is an alkylene radical containing not more than 8 carbon atoms inclusive and the attaching oxygen to carbon bonds are separated by a chain of at least 2 and not more than 3 carbon atoms, 6-methyl-17a -hydroxyprogesterone and the 17-acylate thereof wherein the acyl group is of a hydrocarbon carboxylic acid containing 1-12 carbon atoms inclusive and a process for the preparation thereof which comprises treating a 17a -hydroxyprogesterone 3,20-bis-(alkylene ketal) with a peracid e.g. performic, peracetic, perbenzoic to obtain 5a -6a -oxido-17a -hydroxypregnane-3,20-dione 3,20-bis (alkylene ketal); treating the thus obtained 5a ,6a -oxido-17a -hydroxypregnane-3,20-dione, 3,20-bis(alkylene) ketal) with a lower alkyl metal compound e.g. methyl Grignard reagent to give the corresponding 5a ,17a dihydroxy compound; hydrolysing with aqueous acid the thus obtained diketal to give 5a ,17a -dihydroxy-6b -alkylpregnane 3,20-dione which is dehydrated with an acid or a base to give 6-alkyl-17a -hydroxy-4-pregnene-3,20-dione. The 6-alkyl-17-hydroxyprogesterone so obtained may be esterified with a suitable acid anhydride to produce 17-esters derived from for example benzoic, valeric, hexanoic, phenylacetic, phenylpropionic, propionic and b -cyclopentylpropionic acid.ALSO:Pharmaceutical compositions incorporating 6-alkyl-hydroxyprogesterone esters are employed orally in tablets and in aqueous suspension, and parenterally as a micro-crystalline aqueous suspension. Compositions containing the 17-acetate and 17-b -cyclopentylpropionate are described. Other esters mentioned are the propionate, butyrate, isobutyrate, valerate, isovalerate, hexanoate, heptanoate, octanoate, benzoate, toluate, phenylacetate, phenyl propionate, hemisuccinate, b -dimethylglutarate, cyclohexylformate, decanoate, undecanoate, laurate, undecylenate, acrylate, crotonate, formate or phenoxyacetate.