({5-Cyano-2-[(trifluoroacetyl)amino]phenyl}methyl)(triphenyl)phosphonium chloride → 2-(trifluoromethyl)-1H-indole-5-carbonitrile

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Reaction Steps

({5-Cyano-2-[(trifluoroacetyl)amino]phenyl}methyl)(triphenyl)phosphonium chloride (Intermediate 2, 50.41 g, 95 mmol) was heated in DMF (180 mL) at 140° C. for 7 h. The mixture was cooled to room temperature and the solvents were evaporated. This residue was combined with the corresponding residue from another experiment (wherein Intermediate 2, 7.9 g, 15.05 mmol was heated in DMF (50 mL) at 155° C. for 2 h). The combined residues were azeotroped with toluene (100 mL×2). The resulting residue was treated with diethyl ether (500 mL) and the precipitate filtered and washed with diethyl ether (100 mL). The filtrate was evaporated and the resulting orange oil (˜60 g) was dissolved in DCM (200 mL) and stirred at room temperature. Iso-hexane was added until the cloudyness remained (˜400 mL) and the mixtured stirred for 3 days. No precipitate was observed so the mixture was evaporated and chromatographed (Biotage 75L, eluting with dichloromethane) to give the title compound as a colourless solid (21.7 g);

Provenance & Evidence