Optical Resolution and Optimization of (R,S)-Propranolol Using Dehydroabietic Acid Via Diastereomeric Crystallization

• Published in: Chirality (New York, N.Y.) N.Y.), 2015-02, Vol.27 (2), p.131-136
• Main Authors: Ge, Li, Zhao, Qiongqiong, Yang, Kedi, Liu, Shishi, Xia, Fan
• Format: Article
• Language: English
• Subjects: Chirality; Crystallization; dehydroabietic acid; Methyl alcohol; Optimization; propranolol; Purity; resolution; Response surface methodology; Solvents
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.22401

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. Chirality 27:131–136, 2015. © 2014 Wiley Periodicals, Inc. The optical resolution of (R,S)‐propranolol by the diastereomeric crystallization method was successfully performed using dehydroabietic acid (DHAA) as resolving agent in methanol. And the resolution conditions were optimized employing response surface methodology (RSM).