A method for the preparation of 7α-methoxycephalosporins

Abstract

A method for the preparation of 7α-methoxycephalosporins has been developed. 7β-Phosphoramidodeacetoxycephalosporin (6) and 7β-phosphoramidocephalosporin (14) obtained from the 7β-amino-derivatives (5) and (13), were converted into 7α-methoxy-7β-phosphoramidodeacetoxycephalosporin (7) and 7α-methoxy-7β-phosphoramidocephalosporin (15), respectively, by reaction with LiOMe and Bu^tOCl. Treatment of (7) with BuⁿLi and Et₃N followed by acylation with phenylacetyl chloride gave 7α-methoxy-7β-phenylketenimino-derivative (11), which were easily hydrated to 7α-methoxy-7β-(phenylacetamido)deacetoxycephalosporin (12). Treatment of (15) under similar conditions afforded, contrary to the result obtained with (7), 7α-methoxy-7β-(phenylacetamido)cephalosporin (16), without any of the corresponding ketenimine. This method was also successfully applied to the synthesis of 6α-methoxypenicillins.