反应详情

Trimethylsilylacetamide (6.57 g.) was added to a suspension of 7-amino-3-(benzothiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (3.8 g.) in ethyl acetate (80 ml.), and stirred at room temperature for an hour. On the other hand, thionyl chloride (1.5 g.) was added to a stirred solution of N,N-dimethylformamide (0.92 g.) in ethyl acetate (10 ml.), and stirred under ice-cooling for 30 minutes. To the solution was added 2-methoxyimino-3,3-ethylenedioxybutyric acid (syn isomer, 2.27 g.) and stirred at 5° to 10° C. for 2 hours. Thus obtained activated acid solution was added to the above solution at -30° C. over 45 minutes, and stirred as the same temperature for 2 hours. The resultant mixture was diluted with water (100 ml.) and stirred for 10 minutes. After removing the insoluble substance from the resultant mixture by filtration, the fitrate was extracted with a mixture solvent (200 ml.) of ethyl acetate and methanol (4:1) twice. The insoluble substance obtained above was suspended in the mixed solvent (200 ml.) of ethyl acetate and methanol (4:1), stirred for 30 minutes, and filtered. The filtrate and the above extract were combined, washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in vacuo. Diisopropyl ether was added to the residue and allowed to stand in a refrigerator. After removing the solvent by decantation, the residue was triturated with n-hexane to give 7-[2-methoxyimino-3,3-ethylenedioxybutyramido]-3-(benzothiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 3.7 g.).

1. stirringstirred under ice-
2. temperaturecooling for 30 minutes
3. stirringstirred at 5° to 10° C. for 2 hours
4. additionThus obtained activated acid solution was added to the above solution at -30° C. over 45 minutes
5. stirringstirred as the same temperature for 2 hours
6. stirringstirred for 10 minutes
7. customAfter removing the insoluble substance from the resultant mixture
8. filtrationby filtration
9. extractionthe fitrate was extracted with a mixture solvent (200 ml.) of ethyl acetate and methanol (4:1) twice
10. customThe insoluble substance obtained
11. stirringstirred for 30 minutes
12. filtrationfiltered
13. extractionThe filtrate and the above extract
14. washwashed with saturated aqueous sodium chloride
15. dry with materialdried over magnesium sulfate
16. concentrationconcentrated in vacuo
17. additionDiisopropyl ether was added to the residue
18. customAfter removing the solvent by decantation
19. customthe residue was triturated with n-hexane