反应详情

A mixture of 2-methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid (syn isomer)(1.21 g) and phosphorus oxychloride (3.67 g) in methylene chloride (30 ml) was stirred for two hours at ambient temperature, cooled to 0° C. and thereto was added N,N-dimethylformamide (2.4 ml), followed by stirring for an additional 45 minutes at 0° C. A mixture of 7-amino-2-methyl-3-cephem-4-carboxylic acid (3.0 g) and trimethylsilylacetamide (10 g) in methylene chloride (50 ml) was warmed to make a clear solution. The solution was cooled to -15° C. and added to the above obtained solution, followed by stirring for 30 minutes at 0° C. The reaction mixture was poured into a cold aqueous solution of sodium bicarbonate. The aqueous layer was separated and thereto was added ethyl acetate. The resulting mixture was adjusted to pH 2 with 10% hydrochloric acid and the ethyl acetate layer was separated, dried over anhydrous magnesium sulfate and then evaporated. The residue was triturated with diethyl ether to give a crude product of the title compound (2.2 g). The crude material was dissolved in an aqueous solution of sodium bicarbonate, adjusted to pH 2 with 10% hydrochloric acid. The precipitates were collected by filtration, washed with ice-water and dried to give the title compound (1.6 g), mp. 175° to 180° C. (dec.).

1. temperaturecooled to 0° C.
2. stirringby stirring for an additional 45 minutes at 0° C
3. temperaturewas warmed
4. temperatureThe solution was cooled to -15° C.
5. additionadded to the above obtained solution
6. stirringby stirring for 30 minutes at 0° C
7. customThe aqueous layer was separated
8. additionwas added ethyl acetate
9. customthe ethyl acetate layer was separated
10. dry with materialdried over anhydrous magnesium sulfate
11. customevaporated
12. customThe residue was triturated with diethyl ether