合成路线1

1) The acylation of 7-aminocephalosporanic acid (I) with 2-thienylacetyl chloride (II) gives the acylated compound (III), which is treated with wheat bran enzyme to obtain 3-(hydroxymethyl)-7-(2-thienylacetamido)-3-cephem-4-carboxylic acid (IV). The esterification of (IV) with diphenyldiazomethane affords the corresponding diphenylmethyl ester (V), which is treated with carbonyldiimidazole (CDI) in THF to yield the imidazolecarbonyl ester (VI). The reaction of (VI) with dimethylamine in ethyl acetate/water gives the dimethylcarbamoyl derivative (VII) as a mixture of the 3- and 2-cephem derivatives, which is oxidized with m-chloroperbenzoic acid to the corresponding S-oxides and separated by column chromatography to give pure 3-cephem derivative (VIII). Elimination of the oxide group of (VIII) with PCl3 in DMF affords 3-(dimethylcarbamoyloxymethyl)-7-(2-thienylacetamido)-3-cephem-4-carboxylic acid diphenyl ester (IX), which is treated with PCl5 and pyridine to obtain compound (X) with a free amino group. The acylation of (X) with 2-[2-(tritylamino)thiazol-4-yl]-2(Z)-(trityloxyimino)acetic acid (XI) by means of dicyclohexylcarbodiimide (DCC) gives the fully protected cephem derivative (XII), which is deprotected with trifluoroacetic acid and anisole to yield 7-[2-(2-aminothiazol-4-yl)-2(Z)-(hydroxyimino)acetamido]-3-(N,N-dimethylcarbamoyloxymethyl)-3-cephem-4-carboxylic acid sodium salt (XIII). Finally, this compound is esterified with 1-(isopropoxycarbonyloxy)ethyl iodide (XIV) in DMF.