Hydrochloric Acid → Pilocarpine

Participants

Reaction Conditions

Reaction Steps

0.97 ml of a 15% solution of n-butyllithium in hexane is added at 0° C. to a solution of 0.21 ml of diisopropylamine in tetrahydrofuran. After stirring for 15 minutes and cooling to -78° C., 100 mg of (+)-isopilocarpine dissolved in 1 ml of tetrahydrofuran are added, and the mixture is stirred at -78° C. for 10 hours. After the addition of 1 g of 2,6-di-tert.-butyl-4-methylphenol, warming to room temperature and addition of 15 ml of hydrochloric acid (0.5 N), the layers are separated. The aqueous layer is washed twice with 25 ml of chloroform. Concentration of the organic layer and preparative separation on an HPLC column gives optically pure (+)-pilocarpine which is converted into the pilocarpine nitrate, m.p. 174° C., αD =+81° (c=1.618, water) with nitric acid (65%) in ethanol. Reference1 : R. S. Compagnone, H. Rapoport, J. Org. Chem. 51, 1713-1719 (1986)

Provenance & Evidence