Sodium Carbonate → 7-[2-(2-Formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-cephem-4-carboxylic acid

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Reaction Steps

2-(2-Formamidothiazol-4-yl)-2-carbamoylmethoxyiminoacetic acid (syn isomer, 1.2 g.), N,N-dimethylformamide (0.768 g.), phosphoryl chloride (1.61 g.) and tetrahydrofuran (2.4 ml.) were treated in a similar manner to that of Example 1-(1) to give an activated acid solution. A suspension of 7-amino-3-cephem-4-carboxylic acid (0.89 g.) in a mixture of tetrahydrofuran (8.9 ml.), acetone (4.5 ml.) and water (4.5 ml.) was adjusted to pH 7 to 8 with 20% aqueous sodium carbonate. The activated acid solution was added to the solution at -5° to 0° C. while keeping at pH 7 to 8 and stirred at the same temperature for 30 minutes. The resultant solution was concentrated in vacuo, and water and ethyl acetate were added to the residue. The solution was adjusted to pH 2.5 and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diethyl ether, collected by filtration and dried to give 7-[2-(2-formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 0.95 g.).

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