GB1311454A - Preparation of alkali-metal alpha-carboxypenicillin salts and new forms thereof - Google Patents

Abstract

1311454 Purifying α-carboxypenicillin salts BEECHAM Inc 13 Oct 1971 [22 Oct 1970] 47620/71 Heading C2A α - Carboxypenicillin di(alkali - metal) salts having the general formula wherein R is phenyl, substituted phenyl, thienyl or furyl and M is alkali-metal, are produced by treating the free α-carboxypenicillanic acid (i.e. as above but wherein M is hydrogen) with a basic alkali-metal salt in a water immiscible organic solvent to precipitate an alkali-metal salt of the said acid; and purifying the salt by slurrying it in an organic solvent at a temperature of from 40‹ C. to the boiling point of the solvent and then separating and drying the purified di(alkali metal) salt. The invention includes novel disodium α- carboxybenzylpenicillinate and disodium α- carboxy-3-thenylpenicillinate, which salts are characterized by being in crystalline form and having a water content not greater than 1À5% by weight and 2À5% by weight, respectively. The α-carboxypenicillins treated by the process may be conventionally prepared, e.g. by hydrogenolysis or hydrolysis of corresponding esters such as mono- or di-esters with benzyl or ethyl alcohol or phenols; or by enzymatic cleavage of such esters. Conventionally prepared alkali-metal salts of α-carboxypenicillins may also be used, being first converted to the free acid by acidifying in aqueous solution and extracting the resulting free acid into a waterimmiscible solvent. The basic alkali-metal salt may be a sodium alkoxide (e.g. methoxide, ethoxide or butoxide), a sodium phenoxide (e.g. phenoxide or cresylate) or a sodium carboxylate (e.g. ethylhexoate, ethylbutyrate or lactate). The water-immiscible solvent may be a butanol, amyl or isoamyl alcohol, methyl isobutyl ketone, or methyl, ethyl, propyl or butyl acetate. The preferred slurrying solvent is a C 1 to C 5 aliphatic alcohol. After the slurrying treatment, the salt is separated from the solvent and dried below 80‹ C. The penicillin salts thus produced have well-defined crystalline form, a lower water content, greater stability and a lower content of other alkali-metal salts than conventional alkali metal α-carboxy penicillinates.