反应详情

To a solution of thionyl chloride (3.01 g.) in methylene chloride (45 ml.) were added dimethylformamide (0.928 g.) and 2-(2-formylaminothiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylic acid, (3.71 g.) in turn, and the mixture was stirred for 4 hours at room temperature. Thus obtained mixture was added over 5 minutes to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (3.3 g.) and trimethylsilylacetamide (16.2 g.) in methylene chloride (60 ml.) at room temperature for 40 minutes, with stirring under cooling to -25° to -20° C. The mixture was stirred for 30 minutes at -25° to -20° C., for 30 minutes at -10° to 0° C., and then for 30 minutes at room temperature. To the reaction mixture was added water (30 ml.), and the mixture was stirred for 10 minutes. After a saturated aqueous sodium bicarbonate solution was added to the mixture in order to dissolve the precipitates, the aqueous layer was separated. To the aqueous layer was added ethyl acetate, and the mixture was adjusted to pH 2 with 2 N hydrochloric acid, and then the ethyl acetate layer was separated. The remaining aqueous layer was further extracted with ethyl acetate. The ethyl acetate layers were combined together, washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated. Thus obtained crystalline residue was pulverized in diethyl ether, collected by filtration and then dried to give yellow crystalline powder of 2-methyl-7-[2-(2-formylaminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, which can be represented as 2-methyl-7-[2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, (3.81 g.).

1. additionThus obtained mixture was added over 5 minutes to a solution, which
2. customwas prepared
3. stirringby stirring
4. stirringwith stirring
5. temperatureunder cooling to -25° to -20° C
6. stirringThe mixture was stirred for 30 minutes at -25° to -20° C., for 30 minutes at -10° to 0° C.
7. waitfor 30 minutes at room temperature
8. stirringthe mixture was stirred for 10 minutes
9. dissolutionto dissolve the precipitates
10. customthe aqueous layer was separated
11. additionTo the aqueous layer was added ethyl acetate
12. customthe ethyl acetate layer was separated
13. extractionThe remaining aqueous layer was further extracted with ethyl acetate
14. washwashed with a saturated aqueous sodium chloride solution
15. dry with materialdried over magnesium sulfate
16. concentrationconcentrated
17. filtrationcollected by filtration
18. customdried