| 摘要 |
1,206,626. Acylation of 7-ACA. ELI LILLY & CO. 23 Nov., 1967 [23 Nov., 1966], No. 53320/67. Heading C2A. An improved process for acylating 7-ACA with an acyl halide, comprises contacting the 7-ACA with the acyl halide in the presence of (1) an organic liquid diluent (containing up to 5% by volume of water) that is a non-solvent for said 7-ACA, substantially chemically inert toward said acyl halide and a solvent for the cephalosporin acylation product, and (2) at least one member of the group consisting of urea, thiourea, biuret, dithiobiuret, phenylurea, 1,1-diphenylurea, and phenylthiourea, said component (2) being present in the reaction mixture in an amount ranging from about 0À5 to about 2À0 molar equivalents of said component (2) for each molar equivalent of the acyl halide. Specified organic diluents are dialkyl ketones having 1 to 2 carbon atoms in each alkyl group, e.g. acetone, alkyl esters of 2-7 carbon atoms, e.g. ethyl acetate and a dialkyl sulphoxide of 1-4 carbon atoms in each alkyl group, e.g. dimethyl sulphoxide, or mixtures thereof. For the preparation of sodium 7-(2<SP>1</SP>-thienylacetamido) cephalosporanic acid, diluent (1) is acetone, component (2) is urea, the 2-thienylacetyl chloride is added gradually over 0À5 to 1À5 hours and the sodium salt is formed by the addition of sodium in methanol to the organic liquid containing the free acid. A pharmaceutical composition comprises a cephalosporin prepared as above and a carrier. |
