Skip to main content
SpringerLink
Log in

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

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. M.A. Giembycz, S.K. Field, Drug Des. Dev. Ther. 21(4), 147–158 (2010)

    Google Scholar 

  2. R. Beume, A. Hatelmann, EP2366393, 2006

  3. J. Maus, H. Kastrup, A. Bauhofer, P. Cnota, I. Szelenyi, WO2007071313, 2007

  4. M. Kobayashi, S. Kubo, M. Iwata et al., Int. Immunopharmacol. 11, 732–739 (2011)

    Article  CAS  Google Scholar 

  5. A. Hermann, F. Dieter, G. Beate, et al., WO9501338, 1994

  6. L.A. Sorbera, P.A. Leeson, Castañer. J. Drugs Future 25, 1261–1264 (2000)

    Article  CAS  Google Scholar 

  7. Y.G. Zhong, G.H. Chen, A. Li, S.Y. Li, Chinese J. Pharm. 42(12), 884–886 (2011)

    CAS  Google Scholar 

  8. C.D. Cook, H.R. Jones, H. Kabir, J.D. Lythgoe et al., Org. Process Res. Dev. 2, 157–168 (1998)

    Article  CAS  Google Scholar 

  9. B. Kohl, B. Mueller, W. Palosch, WO2004080967, 2004

  10. Y. Lin, S. Liu, L.F. Sima, L.G. Chen, Res. Chem. Intermed. doi:10.1007/s11164-012-0742-3

  11. G.W. Smith, WO2005041864, 2005

  12. P. Venkata, B. Sarala, M. Nagarajan, et al., WO2006117653, 2006

Download references

Author information

Authors and Affiliations

  1. School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, People’s Republic of China

    Yan Lin, Haofei Qi & Ligong Chen

  2. Tianjin Bohai Chemical Industry Group Co. Ltd, Tianjin, 300040, People’s Republic of China

    Peijun Huang

  3. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, People’s Republic of China

    Donghua Wang

Authors
  1. Yan Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peijun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haofei Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ligong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Donghua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ligong Chen.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 4153 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, Y., Huang, P., Qi, H. et al. Isolation, synthesis and structure confirmation of the impurity in crude roflumilast product. Res Chem Intermed 39, 3111–3115 (2013). https://doi.org/10.1007/s11164-012-0823-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-012-0823-3

Keywords

Search

Navigation