Hydrochloric Acid → Cephalexin

Temperature

-40 °C

38 g of potassium N-(1-ethoxy carbonyl-1-propen-2-yl)-D(-)-α-amino phenyl acetate was suspended in 150 ml of methylene chloride 30 minutes. To thiS 0.5 g of pyridine hydrobromide was added followed by 75 ml of N,N-dimethyl acetamide and 1.4 ml of 2,6-Lutidine. The above mixture was cooled to -40° C. and 17 ml of pivaloyl chloride was added and the reaction mass maintained at -35° to -40° C. for 1 hr. The temperature of the reaction mixture was raised to -20° C. over a period of 30 minutes and cooled rapidly to -65° C. The reaction was buffered with 1.4 ml of 2-ethyl hexanoic acid. A solution of 25 g 7-ADCA and 16 ml in 100 ml of methylene chloride was added to the reaction at -20° C. The reaction was maintained at -40 to -45° C. for 3.5 hrs and warmed to -10° C. over a period of 30 minute. 200 ml of water and 40 ml of HCl were added and the reaction mixture was stirred vigorously. After 30 minutes the upper aqueous phase was filtered and diluted with 50 ml methanol. To this triethylamine (35 ml) was added under stirring at room temperature over a period of 15 minutes to adjust the pH to 5.5. The thick white precipitated mass was slowly cooled to 0° C. and after 1 hr in crystallization filtered, washed with 25 ml ice-water followed by chilled 50% acetone-water (50 ml) and chilled acetone (50 ml). The precipitate was dried at 40° to give 35 g of cephalexin monohydrade.

1. temperaturethe reaction mass maintained at -35° to -40° C. for 1 hr
2. temperatureThe temperature of the reaction mixture was raised to -20° C. over a period of 30 minutes
3. temperaturecooled rapidly to -65° C
4. temperatureThe reaction was maintained at -40 to -45° C. for 3.5 hrs
5. temperaturewarmed to -10° C. over a period of 30 minute
6. filtrationAfter 30 minutes the upper aqueous phase was filtered
7. additiondiluted with 50 ml methanol
8. additionTo this triethylamine (35 ml) was added
9. stirringunder stirring at room temperature over a period of 15 minutes
10. temperatureThe thick white precipitated mass was slowly cooled to 0° C. and after 1 hr in crystallization
11. filtrationfiltered
12. washwashed with 25 ml ice-water
13. temperatureby chilled 50% acetone-water (50 ml)
14. temperaturechilled acetone (50 ml)
15. customThe precipitate was dried at 40°

ORD record

ord-8bf8e36085d2464193d8f4f9b48c0a63

Source dataset

uspto-grants-1999_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05908929