反应详情

In 800 ml of a mixture (1:1) of water and tetrahydrofuran (hereinafter abbreviated as "THF") was suspended 16.9 g of 7β-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid, to which was added, while stirring under ice-cooling, 27.72 g of sodium hydrogencarbonate. To the mixture was then added 29.4 of 2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-methoxyiminoacetyl chloride hydrochloride gradually, followed by stirring for 30 minutes. To the reaction mixture were added 150 ml of water and 200 ml of ethyl acetate, which was shaken and then left standing to form two layers. The aqueous layer was taken, to which was added, while stirring under ice-cooling, 1N HCl to adjust the pH at 7.0. To the resultant was gradually added 18.9 g of sodium N-methyl dithiocarbamate while stirring at room temperature to remove the amino-protecting group (confirming by TLC). To the reaction mixture was added 300 ml of ethyl acetate, and the mixture was shaken and then left standing to form two layers. The aqueous layer was taken and concentrated to a volume of 70 ml under reduced pressure. The concentrate was subjected to a column chromatography using XAD-II (1 l), followed by elution with water. Fractions containing the object compound were collected and concentrated to a volume of 100 ml. To the concentrate was added, while stirring under ice-cooling, 4N HCl to adjust the pH at 2.5. Precipitating crystals were collected by filtration, washed with 100 ml of water, 50 ml of ethyl acetate and 50 ml of THF, followed by drying under reduced pressure to give 19.3 g of 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid.

1. additionto which was added
2. temperaturecooling
3. stirringby stirring for 30 minutes
4. stirringwas shaken
5. waitleft
6. customto form two layers
7. additionwas added
8. stirringwhile stirring under ice-
9. temperaturecooling
10. stirringwhile stirring at room temperature
11. customto remove the amino-
12. additionTo the reaction mixture was added 300 ml of ethyl acetate
13. stirringthe mixture was shaken
14. waitleft
15. customto form two layers
16. concentrationconcentrated to a volume of 70 ml under reduced pressure
17. washfollowed by elution with water
18. additionFractions containing the object compound
19. customwere collected
20. concentrationconcentrated to a volume of 100 ml
21. additionTo the concentrate was added
22. stirringwhile stirring under ice-
23. temperaturecooling
24. customPrecipitating crystals
25. filtrationwere collected by filtration
26. washwashed with 100 ml of water, 50 ml of ethyl acetate and 50 ml of THF
27. customby drying under reduced pressure