Enantioseparation by dual-flow countercurrent extraction: Its application to the enantioseparation of (±)-propranolol

Enantioseparation of (±)-propranolol has been demonstrated by countercurrent extraction with a two-phase system composed of a chloroform solution of didodecyl L-tartrate (100 mM) and an acetate buffer (50 mM, pH 4.4) containing boric acid (100 mM). The free base of (±)-propranolol (1.6 g) was dissolved in the aqueous phase and extracted five times by means of dual-flow countercurrent extraction. After an additional five extractions for recovery, the crude R-(+)- or S-(-)-form was obtained from the aqueous extracts or organic extracts, respectively. They were isolated as their hydrochloride salts with a purity of 89.8% ee (R-form, 385.7 mg) and 88.3% ee (S-form, 429.5 mg), respectively. They were purified to over 99% ee by recrystallizing twice from 1-propanol.