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Continuous flow aminolysis under high temperature and pressure

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Abstract

Under continuous processing conditions, C-N bond formation via SN2 and SNAr substitutions by amines can be an effective preparative method, especially when volatile amines are used under high pressure and temperature. We have demonstrated SN2 substitution of a 2° mesylate with ammonia and opening of an epoxide with benzylamine, and SNAr substitution of a heteroaryl chloride with aqueous ammonia on multi-kg scales. The homogeneous continuous processes offered better process control, higher efficiency, and comparable or superior reaction profiles and yields to batch conditions.

Continuous flow aminolysis under high temperature and pressure

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Acknowledgements

We thank the support of Mr. Remzi Duzguner and Robert A. Giusto for carrying out DSC and TSu process safety testing.

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Author notes

  1. Scott Bader

    Present address: Celgene Corporation, 556 Morris Ave, Summit, NJ, USA

  2. John Lucas

    Present address: Rhodes Technologies, 498 Washington Street, Coventry, RI, USA

  3. John Van Alsten

    Present address: Nitto Denko Avecia Inc, 155 Fortune Blvd., Milford, MA, USA

Authors and Affiliations

  1. Worldwide Research and Development, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA

    Bryan Li, Scott Bader, Steve M. Guinness, Sally Gut Ruggeri, Cheryl M. Hayward, Steve Hoagland, John Lucas, Ruizhi Li, David Limburg, J. Christopher McWilliams, Jeffrey Raggon & John Van Alsten

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  1. Bryan Li
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  2. Scott Bader
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Correspondence to Bryan Li.

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Li, B., Bader, S., Guinness, S.M. et al. Continuous flow aminolysis under high temperature and pressure. J Flow Chem 10, 145–156 (2020). https://doi.org/10.1007/s41981-019-00049-6

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  • DOI: https://doi.org/10.1007/s41981-019-00049-6

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