GB1111214A - Process for preparing semisynthetic penicilins - Google Patents

Abstract

6-Amino-penicillanic acids are acylated in the amino group by treatment with a cyanomethyl ester of the acylating acid. The reaction is suitably effected in an organic or organic-aqueous liquid medium, such as pyridine, acetone, or tetrahydrofuran, in the presence of a catalytic heterocyclic base, such as 2-hydroxy-pyridine, pyrazole, triazole, imidazole or succinimide, by reacting a penicillanic acid salt of a secondary or tertiary amine with a molar excess of the cyanomethyl ester. The product may be purified by extraction of by-products from its aqueous solution with ethyl acetate or ether at neutral or alkaline pH, followed by liberation of the acylated amine from its salt form by addition of acid, and extraction from the acidified aqueous solution with ethyl acetate or ether. The free acid is then precipitated from the solvent by addition of a base (e.g. triethylamine or ammonia) to give the solid salt. Examples are given for acylation of 6-aminopenicillanic acid using cyanomethyl carbobenzoxyamino-acetate, and cyanomethyl alpha-carbobenzoxy-L-amino-beta-phenyl propionate.