Scale-Up and Optimization of a Continuous Flow Carboxylation of N-Boc-4,4-difluoropiperidine Using s-BuLi in THF
- Jean-Paul Kestemonta
- James R. Frostb
- Jérôme Jacqa
- Patrick Pasaua
- Frédéric Perla
- Julien Brownb
- Matthieu Tissot*a
- aUCB Biopharma SPRL, Avenue de l’industrie, 1420 Braine l’Alleud, Belgium
- bUCB, 216 Bath Road, Slough SL1 3WE, United Kingdom
Read the publication that featured this abstractWe report a large-scale carboxylation of N-Boc-4,4-difluoropiperidine (1) enabled by a continuous flow process. The flow process involved N-Boc-directed α-deprotonation using s-BuLi in THF and subsequent trapping with CO2 gas. Flow chemistry enabled the safe and scalable preparation of 400 g of carboxylic acid 2 over the course of a day to support our medicinal chemistry research program.
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R-Series

The Vapourtec R-Series is, quite simply, unrivalled for flow chemistry
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The R-Series is undoubtedly the most versatile, modular flow chemistry system available today.
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The E-Series is a robust and affordable, entry level flow chemistry system designed for reliability and ease of use.