Process for the preparation of 17.beta.-hydroxy-3-oxo-17.alpha.-pregn-4-ene-21-carboxylic acid .gamma.-lactone
AssigneeG. D. Searle & Co.
InventorsHugh L. Dryden, Jr., Mike G. Scaros, Thomas J. Telinski
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Abstract
A new process for the preparation of 17.beta.-hydroxy-3-oxo-17.alpha.-pregn-4-ene-21-carboxylic acid .gamma.-lactone is described herein. The process makes use of androst-4-ene-3,17-dione as the starting material and 17.alpha.-ethynyl-17.beta.-hydroxyandrost-4-en-3-one as an early intermediate.
Claims11
A process for the preparation of 17.beta.-hydroxy-3-oxo-17.alpha.-pregn-4-ene-21-carboxylic acid .gamma.-lactone which comprises:
- a. Reacting 17.alpha.-ethynyl-17.beta.-hydroxyandrost-4-en-3-one with an appropriate vic-glycol containing up to 6 carbon atoms to give the corresponding 3,3-[vic-(lower alkylene)dioxy] 5- or 4-unsaturated compound;
- b. Reacting the ketal with a (lower alkyl) vinyl ether in the presence of an acid catalyst to give the corresponding 17.beta.-[1-(lower alkoxy)ethoxy]-3,3-[vic-(lower alkylene)dioxy]-17.alpha.-ethynylandrost-(5- or 4-) ene;
- c. Reaction of the ketal-acetal with an alkyl lithium or a Grignard reagent followed by treatment with carbon dioxide to give the corresponding salt of 17.beta.-[1-(lower alkoxy)ethoxy]-3,3-[vic-(lower alkylene)dioxy]-17.alpha.-pregn-(5- or 4-)en-20-yne-21-carboxylic acid;
- d. Conversion of the acid salt to the corresponding methyl ester followed by removal of the (lower alkoxy)-ethoxy group to give methyl 3,3-[vic-(lower alkylen)dioxy]-17.beta.-hydroxy-17.alpha.-pregn-(5- or 4-)en-20-yne-21-carboxylate;
- e. Catalytic hydrogenation of the ester followed by acidification to give the desired final product.
A compound of the formula ##STR3## wherein Alk is vic-(lower alkylene).
A compound of the formula ##STR4## wherein Alk is vic-(lower alkylene).
Methyl 3,3-ethylenedioxy-17.beta.-hydroxy-17.alpha.-pregn-5-en-20-yne-21-carboxyl ate.
Dependencies are inferred from the claim text.