Hydrochloric Acid → Pregabalin

Participants

Reaction Conditions

Reaction Steps

The tartarate salt of 3-aminomethyl N,N-diethyl-5-methyl hexanamide (10 grams) was dissolved in water (15 ml) and dichloromethane (25 ml) was added to it. The pH of reaction mixture was adjusted to 9-10 by addition of sodium hydroxide solution (3.0 grams in 3.0 ml of water) and stirred for 10-15 min at 20-25° C. The aqueous and organic layer was separated. The aqueous layer was extracted with dichloromethane. The solvent was distilled off from combined organic layer to obtain a residue. Potassium hydroxide (5.0 gram), water (10 ml) and methanol (10 ml) was added to the obtained residue and heated it to 70-75° C., the reaction was stirred at this temperature for 18 hours. The reaction mixture was cooled to 30° C. and the pH adjusted to 4.0 using concentrated hydrochloric acid. The reaction mixture was heated to 80° C. and stirred for 45 min and filtered. The filtrate was cooled to 5° C. The solid formed was filtered and washed with cool water. The solid was dried at 50-55° C. to yield (S)-Pregabalin.

Provenance & Evidence