反应详情

Phosphorus oxychloride (0.53 ml) was dropwise added to N,N-dimethylformamide (0.42 ml) under ice-cooling. After stirring for 10 minutes at the same temperature, the mixture was cooled until a precipitate appeared. To the suspension was added 2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (1.12 g). The mixture was stirred at the same temperature for 30 minutes to give an activated acid solution. On the other hand, a mixture of 7β-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (1.5 g), N-trimethylsilylacetamide (1.4 g) and bis(trimethylsilyl)acetamide (2.2 g) in tetrahydrofuran (26 ml) was stirred at 30° C. for 30 minutes to give a clear solution. To the clear solution was added the activated acid solution prepared above at -30° C. The mixture was stirred for 30 minutes at -20° C. to -15° C. The mixture was poured into ice-water, adjusted to pH 7.2 with saturated aqueous solution of sodium bicarbonate, and washed with ethyl acetate. The aqueous solution was adjusted to pH 2.5 with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diisopropyl ether to give 7β-[2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (syn isomer) (2.1 g).

1. temperaturecooling
2. temperaturethe mixture was cooled until a precipitate
3. stirringThe mixture was stirred at the same temperature for 30 minutes
4. customto give an activated acid solution
5. stirringwas stirred at 30° C. for 30 minutes
6. customto give a clear solution
7. additionTo the clear solution was added the activated acid solution
8. customprepared above at -30° C
9. stirringThe mixture was stirred for 30 minutes at -20° C. to -15° C
10. washwashed with ethyl acetate
11. extractionextracted with ethyl acetate
12. washThe extract was washed with water
13. dry with materialdried over magnesium sulfate
14. concentrationconcentrated in vacuo
15. customThe residue was triturated with diisopropyl ether