GB1311268A - Process for the isolation of n-benzoyl cephalosporin c - Google Patents

Abstract

1311268 N-Benzoyl-cephalosporin C PFIZER Inc 19 April 1971 [26 Jan 1971] 27118/71 Heading C2A Cephalosporin C is recovered from a cephalosporin C-containing fermentation broth by treating the broth with benzoyl chloride at a pH of 7 to 10 and a temperature of 10 to 15‹ C. to form the N-benzoyl derivative of cephalosporin C, and then acidifying to pH 1 to 3 and extracting the derivative by means of a waterimmiscible solvent. The derivative may then be cleaved to 7-aminocephalosporanic acid, e.g. by conversion to the silyl ester with chlorotrimethylsilane, halogenating the ester with PCl 5 in anhydrous pyridine to form the imino-halide, converting the latter to the imino-ether by treatment with an alcohol and then hydrolysing or alcoholysing the imino-ether to give 7-aminocephalosporanic acid. The fermentation broth may be subjected to a preliminary treatment with 50% sulphuric acid to bring the pH to 2À5 followed by standing at 5‹ C. to room temperature to destroy co-produced penicillin N. Suitable water-immiscible extracting solvents are alcohols (e.g. n-butanol, n-amyl alcohol, n-hexanol or benzyl alcohol), esters, water-immiscible ketones and chlorinated hydrocarbons. The extract is purified with charcoal, concentrated and taken up in acetone. The acetone solution is treated with sodium ethyl hexanoate to precipitate the crystalline monosodium salt of N-benzoyl cephalosporin C, from which free N-benzoyl cephalosporin C is obtained by acidification with sulphuric acid. Reference has been directed by the Comptroller to Specification 847,375.