Dimethylformamide → Methyl 2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carboxylate

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Reaction Steps

A slurry of N-(p-chloro-α-cyanobenzyl)-2,2,2-trifluoroacetamide (10.5 g, 0.04 mol) in toluene under a nitrogen atmosphere is cooled to 10° C., treated with trifluoromethanesulfonic acid (12.0 g, 0.08 mol) over 10-15 minutes, allowed to warm to room temperature and stirred for 3 hours. The reaction is monitored by 19F NMR (DMSO-d6) analysis to show completion of the intermediate salt formation. When formation is complete, the mixture is cooled to 10° C., treated with dimethylformamide, treated with methyl 2-chloroacrylate (7.2 g, 0.06 mol), allowed to warm to room temperature, stirred for 18 hours, and diluted with water and ethyl acetate. The phases are separated and the organic phase is washed with water and concentrated to give a waxy solid residue. Flash column chromatography of the residue on silica gel, packed and eluted with 20% ethyl acetate in heptane gives the title product as a white crystalline solid, 7.6 g (62% yield), mp 123°-125° C. identified by 1H and 19F NMR analyses.

Provenance & Evidence