new cephalosporines useful as intermediate in the preparation of cephalexin and improved process for synthesis of cephalexin

摘要

1,270,633. Esters of desacetoxycephalosporins. ELI LILLY & CO. 18 March, 1970 [18 March, 1969], No. 13101/70. Heading C2A. Novel desacetoxycephalosporin esters having the Formula I wherein Y is hydrogen or in which R is in which RSP1/SP is hydrogen or hydrogen p-toluenesulphonate, are prepared by heating a penicillin sulphoxide ester of Formula II wherein R is as defined above except that RSP1/SP is not hydrogen or hydrogen p-toluenesulphonate, under acid conditions, and if required N- deacylating the product to give a desacetoxycephalosporin ester wherein Y is H which compound is re-acylated with N-protected phenylglycine and the N-protecting group then replaced by hydrogen or hydrogen p-toluenesulphonate. The inventive compounds are intermediates for preparing cephalexin (i.e. 3-methyl-7-(2- amino - 2 - phenylacetamido) - #SP3/SP - cephem - 4- carboxylic acid) by (a) when R is of the Formula (IC) above, removing the p-nitrobenzyl ester group and the RSP1/SP group to give cephalexin; or (b) when R is benzyl or phenoxymethyl, cleaving the 7-phenylacetamido or 7-phenoxyacetamido group to give the 7-amino compound, N-acylating this compound with amino-protected phenylglycine to give the 7-phenylglycylamido - desacetoxy - cephalosporanic acid ester, and removing the amino-protecting group and replacing the ester group by hydrogen to give cephalexin. The starting penicillin sulphoxide esters of Formula II above are prepared by esterifying penicillin V 1-oxide with p-nitrobenzyl bromide (or the chloride promoted with KI) in the presence of triethylamine.