Process for the manufacture of the antibiotic 7-(D- alpha -amino- alpha -phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid (cephalexin) and pharmaceutically acceptable salts thereof

摘要

A process for the manufacture of the antibiotic 7-(D- alpha -amino- alpha -phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid (cephalexin) and pharmaceutically acceptable salts thereof. It consists of reacting an enamine protected potassium salt of D-(-)- alpha -phenyl glycine (Dane salt) with an acid chloride in a twin solvent mixture in the presence of a pyridine derived twin catalytic mixture at -20 to -65 DEG C. The resulting mixed anhydride is condensed with an alkyl guanidinium salt solution of 7-amino desacetoxy cephalosporanic acid (7-ADCA) at -10 DEG C. to -65 DEG C. followed by hydrolytic cleavage of the enamine derivative of the resulting compound with an aqueous mineral acid and precipitation of the antibiotic in the presence of an alcohol as co-solvent. If desired the cephalexin is converted into its pharmaceutically acceptable salts in a known manner.