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.
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