A method for the preparation of substituted malonic acid - monoesters and their use for the production of alpha carboxyl penicillins, cephalosporins or

摘要

1426557 Substituted mono-malonate esters; α-carboxy penicillins BEECHAM GROUP Ltd 10 Sept 1973 [5 Oct 1972] 45936/72 Heading C2C A process for the preparation of a substituted mono-malonate ester of the formula wherein R is an alkyl, cycloalkyl, aryl or aralkyl group which may be substituted, and RSP1/SP is a heterocyclic group, comprises reacting a substituted acetate ester of the formula with an alkyl lithium compound RSP11/SPLi, wherein RSP11/SP is (C 1 -C 5 ) alkyl, in the presence of a secondary amine at a temperature of from - 5‹ to -85‹ C. and then treating the formed lithium ester enolate with CO 2 . The lithium ester enolate is preferably reacted in situ in an ether direct with solid CO 2 . Examples describe the preparation of compounds wherein RSP1/SP is a furyl or thienyl group. α-Carboxy penicillins and α-carboxy cephalosporins can conveniently be prepared by coupling an ester of the invention or a reactive derivative thereof, e.g. the acyl chloride, with 6-amino penicillanic or 7-amino cephalosporanic acid or a derivative thereof and optionally de-esterifying the resulting ester.