反应详情

2,2'-Dithio-bis-5-methyl-1,3,4-thiadiazole (48.09 g) and (Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acid (23.38 g) were suspended in tetrahydrofuran (297 ml) and triphenylphosphine (48.09) was added at 20°-25° C. This mixture was stirred for half an hour to generate 2-mercapto-5-methyl-1,3,4-thiadiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetate in solution. Thereafter, the reaction mixture was cooled to 3°-5° C., diluted with N,N-dimethylacetamide (46.8 ml), water (297 ml) and 7-aminocephalosporanic acid (27.2 g) was added, followed by triethylamine addition in 20 min. The reaction was continued for 3-4 hours at 3°-5° C. Thereafter, acetic acid (18 g) and water (100 ml) were added and the aqueous layer was thoroughly extracted with methylene chloride to remove tetrahydrofuran and other by-products. The aqueous phase containing triethylamine salt of cefotaxime acid was mixed with excess isopropyl alcohol (250 ml) and acidified to pH 2.80 at 0°-5°° C. with hydrochloric acid to precipitate cefotaxime acid. The mixture was then filtered, the solids washed with water, isopropyl alcohol and dried to obtain cefotaxime acid.

1. temperatureThereafter, the reaction mixture was cooled to 3°-5° C.
2. additionwas added
3. extractionthe aqueous layer was thoroughly extracted with methylene chloride
4. customto remove tetrahydrofuran and other by-products
5. additionThe aqueous phase containing triethylamine salt of cefotaxime acid
6. additionwas mixed with excess isopropyl alcohol (250 ml)
7. customacidified to pH 2.80 at 0°-5°° C
8. customwith hydrochloric acid to precipitate cefotaxime acid
9. filtrationThe mixture was then filtered
10. washthe solids washed with water, isopropyl alcohol
11. customdried