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Research on Chemical Intermediates

, Volume 39, Issue 7, pp 3111–3115 | Cite as

Isolation, synthesis and structure confirmation of the impurity in crude roflumilast product

  • Yan Lin
  • Peijun Huang
  • Haofei Qi
  • Ligong ChenEmail author
  • Donghua Wang
Article

Abstract

An impurity was isolated from crude synthesized roflumilast and characterized by 1H NMR, 13C NMR, and HR-MS, which confirmed the structure as N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-3-hydroxybenzamide. To further verify the structure, this compound was synthesized from 4-difluoromethoxy-3-hydroxybenzaldehyde. Comparison of the 1H NMR, 13C NMR, HR-MS, and the HPLC spectrum of the impurity and the authentic sample indicated that this impurity was N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-3-hydroxybenzamide. This demonstrated the significance of monitoring the reaction process of roflumilast.

Keywords

Impurity PDE-4 inhibitor Roflumilast Structure confirmation Synthesis 

Supplementary material

11164_2012_823_MOESM1_ESM.doc (4.1 mb)
Supplementary material 1 (DOC 4153 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Yan Lin
    • 1
  • Peijun Huang
    • 2
  • Haofei Qi
    • 1
  • Ligong Chen
    • 1
    Email author
  • Donghua Wang
    • 3
  1. 1.School of Chemical Engineering and TechnologyTianjin UniversityTianjinPeople’s Republic of China
  2. 2.Tianjin Bohai Chemical Industry Group Co. LtdTianjinPeople’s Republic of China
  3. 3.School of Pharmaceutical Science and TechnologyTianjin UniversityTianjinPeople’s Republic of China

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