6. Industrial Applications of Boric Acid And Boronic Acid-Catalyzed Direct Amidation Reactions

  1. Peter J. Dunn4,
  2. K. K. (Mimi) Hii5,
  3. Michael J. Krische6 and
  4. Michael T. Williams7
  1. Joanne E. Anderson1,
  2. Jannine Cobb1,
  3. Roman Davis1,
  4. Peter J. Dunn2,
  5. Russ N. Fitzgerald1 and
  6. Alan J. Pettman3

Published Online: 23 MAY 2013

DOI: 10.1002/9781118354520.ch06

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

Anderson, J. E., Cobb, J., Davis, R., Dunn, P. J., Fitzgerald, R. N. and Pettman, A. J. (2013) Industrial Applications of Boric Acid And Boronic Acid-Catalyzed Direct Amidation Reactions, 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.ch06

Editor Information

  1. 4

    Pfizer Green Chemistry Lead, Sandwich, Kent, United Kingdom

  2. 5

    Imperial College London, South Kensington, London, United Kingdom

  3. 6

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

  4. 7

    CMC Consultant, Deal, Kent, United Kingdom

Author Information

  1. 1

    GlaxoSmithKline Inc., Research Triangle Park, NC, USA

  2. 2

    Pfizer Global Supply, Pfizer Ltd, Sandwich, Kent, UK

  3. 3

    Chemical Research and Development, Pfizer Ltd, Sandwich, Kent, UK

Publication History

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

ISBN Information

Print ISBN: 9781118155424

Online ISBN: 9781118354520

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Keywords:

  • boric acid;
  • boronic acid;
  • direct amidation reaction;
  • Dr. Reddy's laboratories;
  • efaproxiral intermediate;
  • GlaxoSmithKline (GSK);
  • Pfizer;
  • pharmaceutical intermediates

Summary

Direct amide formation methodology has advantages of atom economy and avoids protection/deprotection steps. Boric acid catalyzed direct amide formation exploits all these advantages in a potentially green and sustainable setting. From an industrial point of view, it is of interest to know if the methodology also works for typical pharmaceutical intermediates, which are often rich in heteroatoms. This chapter presents examples of direct amidation from three companies, a more detailed case history from GlaxoSmithKline (GSK) covering the synthesis of an efaproxiral intermediate and several examples from Dr. Reddy's Laboratories and Pfizer. Water removal using a Dean-Stark (DS) trap, molecular sieves (MS), or an equivalent method, is critical for direct amidation with boric acid or boronic acid catalysis. The chapter ends with a discussion of potential toxicity of boric acid.