反应详情

2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetic acid (syn isomer, 3.6 g.) was added to Vilsmeier reagent prepared from N,N-dimethylformamide (1.1 g.) and phosphoryl chloride (2.3 g.) in dry ethyl acetate (48.4 ml.) at 0° to 5° C. and stirred for 30 minutes to give an activated acid solution. The solution was added to a solution of 7-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (4.4 g.) and trimethylsilylacetamide (11.4 g.) in ethyl acetate (88 ml.) at -10° C. and stirred at -10° to -5° C. for 1.5 hours. After adding water (100 ml.) to the resultant solution, the solution was adjusted to pH 7.0 with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated washed with ethyl acetate and diethyl ether in turn and acidified to pH 2.5 with conc. hydrochloric acid. The precipitates were collected by filtration, washed with water and dried over phosphorus pentoxide to give 7-[2-(2-formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 5.22 g.)

1. customto give an activated acid solution
2. stirringstirred at -10° to -5° C. for 1.5 hours
3. customThe aqueous layer was separated
4. washwashed with ethyl acetate and diethyl ether in turn
5. filtrationThe precipitates were collected by filtration
6. washwashed with water
7. dry with materialdried over phosphorus pentoxide