Scale-Up and Optimization of a Continuous Flow Carboxylation of N‑Boc-4,4-difluoropiperidine Using s‑BuLi in THF

Scale-Up and Optimization of a Continuous Flow Carboxylation of N‑Boc-4,4-difluoropiperidine Using s‑BuLi in THF

We 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 carb...

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Veröffentlicht in:Organic process research & development 2022-03, Vol.26 (3), p.635-639
Hauptverfasser: Kestemont, Jean-Paul, Frost, James R, Jacq, Jérôme, Pasau, Patrick, Perl, Frédéric, Brown, Julien, Tissot, Matthieu
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Sprache:eng
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Zusammenfassung:We 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.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.1c00092