DE2242684

1399349 Acylation of cephalosporin esters LILLY INDUSTRIES Ltd 7 Dec 1972 [11 Sept 1971] 42454/71 Heading C2C In a method for the acylation of the p-nitrobenzyl ester of 7-aminocephalosporanic acid or 7-aminodesacetoxycephalosporanic acid with a mixed anhydride, the acylation is carried out at a temperature between - 15‹ and - 50‹ C. and preferably between - 25‹ and - 45‹ C. The mixed anhydride may be of Formula I wherein R is C 1-4 alkyl ; R11 is C 1-8 alkyl, or of Formula II or III in which W is S or O, Z is H, lower alkyl (C 1-3 ), CF 3 -, C 1-3 alkoxy, -OY, nitro, -NHR11, C 1-3 alkylamino, di-(C 1-3 )alkylamino, Cl, Br or F; X is -(CH 2 ) n -, -OCH 2 -, n is 0 or 1; Y is C 1-4 alkyl, benzyl, substituted benzyl or C 1-4 alkanoyl; and R111 is of Formula VI, VII, VIII, IX or X A method of preparing cephalexin comprises acylating the p-nitrobenzyl ester of 7-aminodesacetoxycephalosporanic acid with a nitrogenblocked mixed anhydride of D-phenylglycine, the acylation being conducted between - 15‹ and - 50‹ C. and being followed by removal of the amino and carboxyl blocking groups. Suitable amino blocking groups are t-butoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl or an enamine formed by reacting the phenylglycine with an alkyl acetoacetate.