10. Challenge and Opportunity in Scaling-Up Metathesis Reaction: Synthesis of Ciluprevir (BILN 2061)

  1. Peter J. Dunn2,
  2. K. K. (Mimi) Hii3,
  3. Michael J. Krische4 and
  4. Michael T. Williams5
  1. Nathan Yee,
  2. Xudong Wei and
  3. Chris Senanayake

Published Online: 23 MAY 2013

DOI: 10.1002/9781118354520.ch10

Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries

Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries

How to Cite

Yee, N., Wei, X. and Senanayake, C. (2013) Challenge and Opportunity in Scaling-Up Metathesis Reaction: Synthesis of Ciluprevir (BILN 2061), in Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries (eds P. J. Dunn, K. K. (. Hii, M. J. Krische and M. T. Williams), John Wiley & Sons, Inc., Hoboken, New Jersey. doi: 10.1002/9781118354520.ch10

Editor Information

  1. 2

    Pfizer Green Chemistry Lead, Sandwich, Kent, United Kingdom

  2. 3

    Imperial College London, South Kensington, London, United Kingdom

  3. 4

    University of Texas at Austin, Austin, Texas, United States of America

  4. 5

    CMC Consultant, Deal, Kent, United Kingdom

Author Information

  1. Chemical Development, Boehringer Ingelheim Pharmaceutical, Inc., Ridgefield, CT, USA

Publication History

  1. Published Online: 23 MAY 2013
  2. Published Print: 8 APR 2013

ISBN Information

Print ISBN: 9781118155424

Online ISBN: 9781118354520

SEARCH

Keywords:

  • ciluprevir;
  • ring-closing metathesis (RCM) reaction

Summary

This chapter describes the challenges and opportunities involved in developing a practical and efficient chemical process for ciluprevir through ring-closing metathesis (RCM). In particular, it highlights the efforts in developing the first scale-up of RCM reaction for potential commercialization. During the course of these studies, a number of critical parameters for the RCM reaction, such as the nature of the precatalysts, initiation site, and conformations of substrate/products, were studied which led to the successful development of a practical process for scaling up the RCM reaction. Also, the second generation ciluprevir process represents the optimal convergent strategy for the assembly of ciluprevir for its potential commercialization.