Hydrochloric Acid → Cephalexin

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence