We describe the total flow synthesis of the widely prescribed anti-inflammatory COX-2 inhibitor Celecoxib from 2-bromo-3,3,3-trifluoropropene, as a convenient and available trifluoromethyl building block, to generate trifluoropropynyl lithium and to trap it immediately with an aldehyde. Oxidation of the obtained alcohol into ketone followed by condensation with 4-sulfamidophenylhydrazine afforded the targeted drug with full regioselectivity. It is noteworthy that the quality of these flow reactions (50% overall yield within 1 h cumulated residence time over 3 steps) directly furnished the target API and intermediates with excellent purity.
Supplementary information: The online version contains supplementary material available at 10.1007/s41981-021-00205-x.
Keywords: Active pharmaceutical ingredients; NSAID; Organofluorine chemistry; Organolithium chemistry; Oxidation.
© Akadémiai Kiadó 2021.