(<i>S</i>)-3-Methyl-2-phenylbutylamine, a Versatile Agent to Resolve Chiral, Racemic Carboxylic Acids¹

Abstract

(S)-Ibuprofen 2, (S)-ketoprofen 3, and (S)-naproxen 4 are all obtained by optical resolution of the respective racemates with (S)-3-methyl-2-phenylbutylamine (PBA) 1: (S)-2, 98.7% ee, 39.8% yield; (S)-3, 99.4% ee, 36.7% yield; (S)-4, 99.2% ee, 35.1% yield. (S)-PBA 1 is also useful in resolving other racemic carboxylic acids of pharmaceutical importance; (R)-2-hydroxy-4-phenylbutanoic acid (HPBA) 5, a key intermediate for ACE inhibitors such as benazapril 7, and (S)-2-benzylsuccinic acid (BSA) 6, a key intermediate for hypoglycemic KAD-1229 8, are obtained in 99% ee and 34.4% yield, and in 99% ee and 32.2% yield, respectively.