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Updated: Jul 24, 2025

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Published on: November 15, 2017
Synthesis of the Brivaracetam Employing Asymmetric Photocatalysis and Continuous Flow Conditions
Marcelo S Franco1, Rodrigo C Silva2, Gabriel H S Rosa2
1Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Florianópolis, Santa Catarina 88040-900, Brazil.
Abstract:
An original total synthesis of the antiepileptic drug brivaracetam (BRV) is reported. The key step in the synthesis consists of an enantioselective photochemical Giese addition, promoted by visible-light and the chiral bifunctional photocatalyst Δ-RhS. Continuous flow conditions were employed to improve the efficiency and allow an easy scale-up of the enantioselective photochemical reaction step. The intermediate obtained from the photochemical step was converted into BRV by two different pathways, followed by one alkylation and amidation, thus giving the desired active pharmaceutical ingredients (API) in 44% overall yield, 9:1 diastereoisomeric ratio (dr) and >99:1 enantiomeric ratio (er).
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