Bulletin of the Korean Chemical Society

  • 제34권2호
  • /
  • Pages.549-552
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  • 2013
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  • 0253-2964(pISSN)
  • /
  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
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A Novel Synthetic Method for Bepotastine, a Histamine H1 Receptor Antagonist

  • 투고 : 2012.10.10
  • 심사 : 2012.11.22
  • 발행 : 2013.02.20
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⟨ 이전 논문 다음 논문 ⟩

초록

An efficient and alternative synthesis of enantiomerically pure (+)-(S)-4-(4-((4-chlorophenyl)(pyrid-2-yl)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) with 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.

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참고문헌

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  3. Structural Insight into Enantioselective Inversion of an Alcohol Dehydrogenase Reveals a “Polar Gate” in Stereorecognition of Diaryl Ketones vol.140, pp.39, 2013, https://doi.org/10.1021/jacs.8b08640
  4. Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N-Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent vol.20, pp.4, 2013, https://doi.org/10.1021/acs.orglett.7b03878
  5. Highly Enantioselective Hydrogenation of Non-ortho-Substituted 2-Pyridyl Aryl Ketones via Iridium-f-Diaphos Catalysis vol.21, pp.14, 2019, https://doi.org/10.1021/acs.orglett.9b01415
  6. Light-induced metal-free transformations of unactivated pyridotriazoles vol.10, pp.36, 2019, https://doi.org/10.1039/c9sc02448d