反应详情

Vilsmeier reagent was prepared from phosphorus oxychloride (1.4 g) and N,N-dimethylformamide (0.65 g) in ethyl acetate (2.6 ml) in a usual manner. 2-t-Butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3-yl)acetic acid (syn isomer) (2.1 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (20 ml) under ice-cooling and the mixture was stirred for 30 minutes at the same temperature to prepare an activated acid solution. 7-Amino-3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (3.0 g) was dissolved to the solution of sodium bicarbonate (2.1 g) in water (25 ml) and acetone (25 ml). To the solution was added the above activated acid solution at -3° to 3° C. and the solution was stirred for 30 minutes under keeping the pH 7 to 8 with 20% an aqueous solution of sodium carbonate. Ethyl acetate and water were added to the reaction mixture and the mixture was adjusted to pH 2.0 with 10% hydrochloric acid. The separated organic layer was washed with saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated to give 7-[2-t-butoxycarbonylmethoxyimino-2-(1,2,4-thiadiazol-3 -yl)acetamido]-3-(tetrazolo[1,5-b]pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (4.07 g).

1. temperaturecooling
2. customto prepare an activated acid solution
3. additionTo the solution was added the above activated acid solution at -3° to 3° C.
4. stirringthe solution was stirred for 30 minutes
5. washThe separated organic layer was washed with saturated aqueous solution of sodium chloride
6. dry with materialdried over magnesium sulfate
7. customevaporated