Cinchonidine → Cinchonidine

Participants

Reaction Conditions

Reaction Steps

L-cinchonidine (30.2 g, 0.103 mol) is added to crude cyclohexyl-hydroxy-thiophen-2-yl-acetic acid (49.3 g, 103 mol assuming 50% purity of crude) followed by toluene (2.2 litres) and the mixture is heated to reflux for 70 minutes. The resulting solution is allowed to cool slowly and at 65° C., the solution is seeded. After further cooling to 40° C., the solution is placed in the fridge overnight. The resulting solid is filtered, washed with toluene and dried in vacuo. The recrystallisation process from toluene is repeated for a second time with seeding occurring at 85° C. to afford the titled compound as a salt of L-cinchonidine in 98% enantiomeric excess. The salt is added to a stirred mixture of 1M HCl (40 ml) and diethyl ether (500 ml) and stirring continues until a solution forms. The organic portion is separated, washed with brine (400 ml), dried over MgSO4 and concentrated in vacuo to give the titled compound in 98% enantiomeric excess.

Provenance & Evidence