Synthesis of the Brivaracetam Employing Asymmetric Photocatalysis and Continuous Flow Conditions
Category
Published on CMKC
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).
Journal
ACS Omega. Volume 8, 2023, 23008–23016
DOI
10.1021/acsomega.3c02134
Type of publication
Peer-reviewed journal
Affiliations
- Universidade Federal de Santa Catarina
- Universidade Federal de São Carlos
Article Classification
Research Article
Classification Areas
- Intermediate
- API