PREPARATION D'UNE 7-AMINO CEPHALOSPORINE

1,266,252. Preparing 3-methyl-7-aminocephalosporins. ELI LILLY & CO. 10 March, 1970 [10 March, 1969], No. 11343/70. Heading C2A. 3 - Methyl - 7 - amino - cephalosporins of formula wherein R1 is hydrogen or an easily removable carboxyl-protecting group, are prepared by treating a corresponding 3-methyl-7-acylamino cephalosporin with at least 1 molar proportion of a solvent of formula R11-OH at 0-125‹ C. in the presence of at least 0À25 equivalent of an acid having a pKa below 3, R11 being hydrogen, methyl, ethyl or propyl and the acylating group in the starting cephalosporin having the formula or in which Q is hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, cyano, nitro, hydroxy, chloro, bromo or fluoro; Y is hydrogen or hydroxy; X is oxygen or sulphur; m is 0, 1 or 2; and n is 1, 2 or 3. The carboxyl-protecting group may be an easily removable esterifying group; preferred starting materials are those wherein the acylating group is benzyl or phenoxymethyl. When the solvent R11-OH is water, an inert watermiscible organic co-solvent is preferably added to maintain the reactants and products in solution. Suitable acids are p-toluenesulphonic acid, methanesulphonic acid, trifluoroacetic acid, hydrochloric acid, phosphoric acid and sulphuric acid. The product may be obtained in the form of the salt of the acid used, e.g. pnitrobenzyl - 3 - methyl - 7 - amino - A3 - cephem- 4 - carboxylate p - toluenesulphonic acid salt monohydrate.