反应详情

40 g of 7-amino-3-vinyl-3-cephem-4-carboxylic acid (AVNA, 0.177 mol) was added to 400 ml of tetrahydrofuran under nitrogen atmosphere followed by 78 g of O-acetyl thioester (0.206 mol, prepared in Example 1) and 200 ml of water with stirring. Cooled the reaction mass to 15–20° C. To this reaction mixture, 20 g of triethylamine was added slowly at pH ˜8.5. Stirring was continued and progress of the reaction was monitored by qualitative HPLC till AVNA was less than 1%. At this stage 400 ml of methylene dichloride was added and stirred for further 15 min at 20–25° C. 200 ml of water was added and stirred the reaction mass for 15 min at 20–25° C. Separated the layers and to the aqueous layer, 20% w/v aqueous potassium carbonate solution was added and maintained pH at 8.1–8.2 at 20–25° C. Thereafter, 26.4 g of ammonium chloride was added in one lot at 20–25° C. and continued maintaining the pH between 8.0 to 8.2 by addition of 20% w/v aqueous potassium carbonate solution. The progress of reaction was monitored by qualitative HPLC till O-acetyl cefdinir is less than 0.5%. Adjusted the pH of reaction mass to 2.4–2.5 with conc. sulfuric acid maintaining temperature between 35° to 40° C. The precipitated product was filtered and dried at 40–45° C. under reduced pressure till moisture content was ≦2% wiw. 44 g of product was obtained in 99.3% purity (by HPLC).

1. temperatureCooled the reaction mass to 15–20° C
2. stirringStirring
3. stirringstirred for further 15 min at 20–25° C
4. stirringstirred the reaction mass for 15 min at 20–25° C
5. customSeparated the layers
6. additionwas added
7. temperaturemaintained pH at 8.1–8.2 at 20–25° C
8. additionThereafter, 26.4 g of ammonium chloride was added in one lot at 20–25° C.
9. temperaturecontinued maintaining the pH between 8.0 to 8.2
10. additionby addition of 20%
11. customThe progress of reaction
12. filtrationThe precipitated product was filtered
13. customdried at 40–45° C. under reduced pressure till moisture content