Glaxo Group Limited

Gennaro Maruzzelli

Marco Croci

Improvements in or relating to the manufacture of semi-synthetic penicillin antibiotics are described. More particularly an improved process for the preparation of a 6.beta.-acylamino penicillanic acid antibiotic product is described in which 6.beta.-aminopenicillanic acid (6-APA) is reacted in an inert solvent with a silylating agent to form a silylated compound of formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a tri(C.sub.1-6 alkyl)silyl group, and R.sup.2 represents a tri(C.sub.1-6 alkyl)silyl group and the compound of formula (I) is thereafter contacted with an acyl chloride or protected acyl chloride corresponding to the desired 6.beta.-acylamino group, the silyl groups are cleaved and the desired antibiotic product is recovered, silylation being effected using a tri(C.sub.1-6 alkyl) silylurea or tri(C.sub.1-6 alkyl) halosilane and the compound of formula (I) produced being reacted without intermediate isolation with the acyl chloride or protected acyl chloride, wherein acylation is effected in the presence of a hydrogen halide acceptor mixture comprising in excess of 0.15 and preferably up to 3.00 moles of urea per mole of 6-APA; in excess of 0.15, and preferably up to 1.30 moles of bis-tri-(C.sub.1-6 alkyl)silylurea per mole of 6-APA; and in excess of 0.25, and preferably up to 3.30 moles of tri-(C.sub.1-6 alkyl)-ammonium halide per mole of 6-APA. The process is especially useful for the preparation of ampicillin and amoxycillin in high yield and high purity.

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Milan, Italy

Gennaro Maruzzelli