Optical Resolution and Optimization of (<i>R</i>,<i>S</i>)‐Propranolol Using Dehydroabietic Acid Via Diastereomeric Crystallization

Abstract

The optical resolution of (R,S)-propranolol by the diastereomeric crystallization method was successfully performed using dehydroabietic acid (DHAA) as the resolving agent in methanol. The three important parameters: DHAA amount, solvent (methanol) amount, and crystallization temperature of diastereomeric salts were optimized employing the response surface methodology (RSM). When maintaining a lower limit of 95% for the purity of (S)-propranolol, the optimal resolution conditions were a DHAA/(R,S)-propranolol molar ratio of 1.1, solvent/(R,S)-propranolol ratio of 16.2 mL.g(-1) , and crystallization temperature of -5 °C. The desired (S)-propranolol was prepared with 94.8% optical purity and 72.2% yield under the optimal conditions.