Pyridine → 4-cyano-N-[2-ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethyl-propyl)-6-methyl-phenyl]-3-methyl-benzamide

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Reaction Steps

To a solution of 4-cyano-3-methyl-benzoic acid (6.64 g, 41.20 mmol) (prepared according to Bioorganic & Medicinal Chemistry Letters 2004, 14(17), 4585-4589 or EP 1,512,687) and N,N-dimethylformamide (“DMF”) (few drops) in dichloromethane (200 ml) under an atmosphere of nitrogen was added oxalyl chloride (4.18 ml, 49.44 mmol). The reaction mixture was stirred for one hour at ambient temperature and then for 1.5 hours at 60° C. The reaction mixture was concentrated and the residue dissolved in tetrahydrofuran (200 ml). The solution was added drop-wise to a solution of 2-methyl-6-ethyl-4-(heptafluoro-prop-2-yl)-aniline (prepared according to EP 1,006,102) (10.910 g, 30.90 mmol) and pyridine (3.31 ml, 41.20 mmol) in tetrahydrofuran (200 ml). The reaction mixture was stirred for 16 hours at 90° C. Then the reaction mixture was poured into aqueous sodium hydrogen carbonate (1M) and the mixture extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by column chromatography (eluent: ethyl acetate/cyclohexane 1:3) to give the desired compound (15.34 g, 94% yield). 1H-NMR (400 MHz, CDCl3): 7.90 (1H, s), 7.78 (2H, m), 7.53 (1H, s), 7.39 (2H, s), 2.67 (5H, s), 2.35 (3H, s), 1.16 (3H, t) ppm.

Provenance & Evidence