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

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.

• Sonia De Angelis^{1, 2}
• Paolo Celestini³
• Rosa Purgatorio¹
• Leonardo Degennaro^{1, 2}
• Gabriele Rebuzzini³
• Renzo Luisi^{1, 2}
• Claudia Carlucci^{1, 2}

• ¹Department of Pharmacy - Drug Sciences, University of Bari "A. Moro" Via E. Orabona 4, Bari, Italy
• ²Flow Chemistry and Microreactor Technology FLAME-Lab, Bari, Italy
• ³COSMA S.p.A, Ciserano Italy

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