| 摘要 |
1312232 Preparing 3-methyl-cephalosporanic acid esters GLAXO LABORATORIES Ltd 10 March 1970 [11 March 1969 22 Sept 1969] 12866/69 and 46622/69 Heading C2A 7# - Acylamido - 3 - methyl - cephalosporanic acid esters are prepared by heating a 6#-acylamido-penicillanic acid 1-oxide ester in a reaction-inert organic solvent in the presence of a salt of an amine base of pKb not less than 4 with an acid, which salt may be formed in situ in the reaction mixture. The amine base is preferably an unsaturated heterocyclic tertiary amine, e.g. pyridine, quinoline, iso-quinoline or benzimidazole, which heterocycles may be substituted by C 1 -C 6 alkyl, halogen, acyl, acylamido, cyano, carboxy or aldoximino groups. Another preferred base is aniline or an N-alkyl aniline; the aniline being optionally nuclear-substituted by halogen, alkyl, hydroxy, alkoxy, nitro or carboxy groups. The acid may be an organic sulphonic acid, e.g. hydrocarbyl or pyridyl sulphonic acid; or trifluoracetic acid, or a phosphorus acid, e.g. ortho-, pyro- or poly-phosphoric acid, phosphorous acid or a phosphonic acid. The latter can be aliphatic, araliphatic or aryl phosphonic acids wherein the hydrocarbon moiety may be substituted by halogen, alkyl or nitro groups. When the salt is formed in situ, either the base or the acid may be present in excess of the equivalent amount needed for neutralization or else equivalent proportions of each may be used. The reaction is preferably conducted in one of the solvents used in Specification 1,299,734; the isolation procedures for the product and the procedure used for preparing the penicillin 1- oxide starting material are also similar to the procedures as described in the said Specification. |
