Hydrochloric Acid → 7-[2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

Participants

Reaction Steps

2-(2-Formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid (syn isomer, 1.62 g.) was added to a solution of N,N-dimethylformamide (432 mg.) and phosphoryl chloride (905 mg.) in tetrahydrofuran (16 ml.) and treated in a similar manner to that of Example 6-(1). The solution was added to a solution of 7-amino-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (3.0 g.) and triethylamine in 50% aqueous acetone (30 ml.) at -5° to -3° C. and pH 7 to 7.5 and stirred for 30 minutes. Ethyl acetate was added to the resultant solution and adjusted to pH 2.0 with 10% hydrochloric acid. After removing the insoluble substance by filtration, water and ethyl acetate were added to the filtrate. The ethyl acetate layer was separated and washed with saturated sodium chloride solution. The solution was dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diethyl ether and the precipitates were collected by filtration to give 7-[2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2.93 g.).

Provenance & Evidence