Scalable Flow Electrochemical Alcohol Oxidation: Maintaining High Stereochemical Fidelity in the Synthesis of Levetiracetam

An electrochemical flow process has been developed for an alcohol oxidation step in the synthesis of the generic epilepsy drug levetiracetam. A crucial metric in this process is the retention of high enantiomeric purity as the oxidation of the primary alcohol to the carboxylic acid proceeds via an e...

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Bibliographic Details
Published in:Organic process research & development 2021-12, Vol.25 (12), p.2601-2607
Main Authors: Zhong, Xing, Hoque, Md Asmaul, Graaf, Matthew D, Harper, Kaid C, Wang, Fei, Genders, J. David, Stahl, Shannon S
Format: Article
Language:English
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Summary:An electrochemical flow process has been developed for an alcohol oxidation step in the synthesis of the generic epilepsy drug levetiracetam. A crucial metric in this process is the retention of high enantiomeric purity as the oxidation of the primary alcohol to the carboxylic acid proceeds via an epimerizable aldehyde intermediate. Here, three different reactor configurations are compared: undivided batch, undivided flow, and divided flow cells. The divided flow cell accesses the highest rate, throughput, and enantiomeric fidelity among the three configurations. This approach is showcased in a 200-g scale process that retains ≥97% enantiomeric purity and highlights a unique advantage of flow electrolysis.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.1c00036