Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene

• Maria Ivanova¹
• Julien Legros¹
• Thomas Poisson^1,2
• Philippe Jubault¹

• ¹INSA Rouen, CNRS, UNIROUEN, COBRA, Normandie Univ, 76000 Rouen, France
• ²Institut Universitaire de France, 1 Rue Descartes, 75231 Paris, France

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.

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