Trifluoromethanesulfonic acid → 2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile

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Reaction Steps

A mixture of N-(p-chloro-α-cyanobenzyl)-2,2,2-tri-fluoroacetamide (10.5 g, 0.04 mol) and toluene is cooled to 5°-10° C. under a nitrogen atmosphere, treated with trifluoromethanesulfonic acid (12.0 g, 0.08 mol) over a 20 minute period, allowed to warm to room temperature and held at 25° C. for 3 hours. The formation of the intermediate 5-amino oxazole salt is monitored by 19F NMR (DMSO-d6). When the intermediate salt formation is complete, the mixture is cooled below 20° C., treated with dimethylformamide and 2-chloroacrylonitrile (5.25 g, 0.06 mol), held at 25° C. for 16-18 hours, and treated with ethyl acetate and water. The phases are separated and the organic phase is washed with water and concentrated in vacuo to give a solid residue. Flash column chromatography of the residue on silica gel, packed and eluted respectively with 15% and 20% ethyl acetate in heptane gives the title product as pale yellow crystals, 6.14 g (57% yield), mp 237°-240° C., identified by HPLC and NMR analyses.

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