反应详情

温度

40 °C

Phosphorus oxychloride (0.65 g.) was added under ice-cooling to dry dimethylformamide (0.31 g.) and the mixture was stirred for 30 minutes at 40° C. Dry ethyl acetate (15 ml.) was added thereto and to the suspension was added under ice-cooling 2-methoxyimino-2-(1,2,3-thiadiazol-4-yl)-acetic acid (syn isomer) (0.65 g.), after which the resulting mixture was vigorously stirred for 30 minutes at the same temperature to give a solution. On the other hand, trimethylsilylacetamide (4.20 g.) was added to a suspension of 7-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.20 g.) in dry ethyl acetate (50 ml.), and the mixture was stirred for 2.5 hours at ambient temperature. To this suspension was at a time added at -20° C. the above-obtained ethyl acetate solution, and the resulting mixture was stirred for 1.5 hours at the same temperature. The reaction mixture was extracted after addition of ethyl acetate (70 ml.) and water (35 ml.). The organic layer was extracted with a sodium bicarbonate aqueous solution (35 ml.). To the aqueous extract was added ethyl acetate (70 ml.), and the mixture was adjusted. to pH 2.0 with conc. hydrochloric acid with stirring and then the ethyl acetate layer was separated. The ethyl acetate layer was washed with a sodium chloride aqueous solution and dried over magnesium sulfate. The solvent was distilled off to give white powder of 7-[2-methoxyimino-2-(1,2,3-thiadiazol-4-yl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.36 g.).

1. additionto the suspension was added under ice-
2. stirringafter which the resulting mixture was vigorously stirred for 30 minutes at the same temperature
3. customto give a solution
4. stirringthe mixture was stirred for 2.5 hours at ambient temperature
5. stirringthe resulting mixture was stirred for 1.5 hours at the same temperature
6. extractionThe reaction mixture was extracted
7. additionafter addition of ethyl acetate (70 ml.) and water (35 ml.)
8. extractionThe organic layer was extracted with a sodium bicarbonate aqueous solution (35 ml.)
9. extractionTo the aqueous extract
10. additionwas added ethyl acetate (70 ml.)
11. stirringto pH 2.0 with conc. hydrochloric acid with stirring
12. customthe ethyl acetate layer was separated
13. washThe ethyl acetate layer was washed with a sodium chloride aqueous solution
14. dry with materialdried over magnesium sulfate
15. distillationThe solvent was distilled off