Development of a continuous flow synthesis of propranolol: tackling a competitive side reaction

Journal of Flow Chemistry volume 9, pages231–236(2019)Cite this article

Abstract

This work reports the preparation of propranolol according to a flow process. Propranolol has been prepared paying attention to tackle the formation of the by-product tertiary amine, resulting from an additional ring opening of the starting epoxide. Remarkably, the use of catalytic amount of water resulted beneficial for the yield and purity of the desired propranolol, and to substantially reducing the amount of tertiary amine byproduct. The high concentration of the solutions allowed for a productivity of several grams/h.

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Acknowledgments

We are grateful to Prof. Saverio Cellamare for the precious contribution in the technical support.

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Affiliations

  1. Department of Pharmacy — Drug Sciences, University of Bari “A. Moro” Via E. Orabona 4, 70125, Bari, Italy

    Sonia De Angelis, Rosa Purgatorio, Leonardo Degennaro, Renzo Luisi & Claudia Carlucci

  2. Flow Chemistry and Microreactor Technology FLAME-Lab, Bari, Italy

    Sonia De Angelis, Leonardo Degennaro, Renzo Luisi & Claudia Carlucci

  3. COSMA S.p.A, Via Colleoni 15/17, 24040, Ciserano, BG, Italy

    Paolo Celestini & Gabriele Rebuzzini

Authors
  1. Sonia De Angelis
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  2. Paolo Celestini
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  3. Rosa Purgatorio
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  4. Leonardo Degennaro
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  5. Gabriele Rebuzzini
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  6. Renzo Luisi
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  7. Claudia Carlucci
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Corresponding authors

Correspondence to Gabriele Rebuzzini or Renzo Luisi.

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De Angelis, S., Celestini, P., Purgatorio, R. et al. Development of a continuous flow synthesis of propranolol: tackling a competitive side reaction. J Flow Chem 9, 231–236 (2019). https://doi.org/10.1007/s41981-019-00047-8

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Keywords

  • Propranolol
  • Tertiary amines
  • Ring opening
  • Flow chemistry
  • HPLC