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

  • Sonia De Angelis
  • Paolo Celestini
  • Rosa Purgatorio
  • Leonardo Degennaro
  • Gabriele RebuzziniEmail author
  • Renzo LuisiEmail author
  • Claudia Carlucci
Full Paper


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.


Propranolol Tertiary amines Ring opening Flow chemistry HPLC 



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

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

41981_2019_47_MOESM1_ESM.pdf (2.1 mb)
ESM 1 (PDF 2177 kb)


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Copyright information

© Akadémiai Kiadó 2019

Authors and Affiliations

  1. 1.Department of Pharmacy — Drug SciencesUniversity of Bari “A. Moro” Via E. Orabona 4BariItaly
  2. 2.Flow Chemistry and Microreactor Technology FLAME-LabBariItaly
  3. 3.COSMA S.p.ACiseranoItaly

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