A Novel Synthetic Method for Bepotastine, a Histamine H1 Receptor Antagonist

Tae Hee Ha, Kwee-Hyun Suh, Gwan Sun Lee
2013 Bulletin of the Korean Chemical Society (Print)  
An efficient and alternative synthesis of enantiomerically pure (+)-(S)-4-(4-((4-chlorophenyl)(pyrid-2yl)methoxy]piperidin-1-yl)butanoic acid, bepotastine (1) is described. The key resolution of (R/S)-bepotastine l-menthyl ester (3) is achived via diastereomeric salt crystallization using N-benzyloxycarbonyl-L-aspartic acid (NCbzLAA) as the resolving agent to provide (S)-bepotastine l-menthyl ester (S)-3. Hydrolysis of (S)bepotastine l-menthyl ester (S)-3 afforded the desired bepotastine (1)
more » ... h good yields and enantiopurity (> 99%). Finally, bepotastine besilate (4) and bepotastine calcium (5) are achived by salt formation of bepotastine (1) with benzene sulfonic acid and calcium salt respectively. The reaction conditions were optimized to make suitable for commercial scale production.
doi:10.5012/bkcs.2013.34.2.549 fatcat:hb7yf6kierau3frgozavxsi56m