Acetic Acid → 3-Chloro-5-((1,2-dihydro-2-oxo-4-(trifluoromethyl)-3-pyridinyl)oxy)benzonitrile

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Reaction Steps

To a round bottom flask charged with 3-(3-bromo-5-chlorophenoxy)-4-(trifluoromethyl)pyridin-2(1H)-one (3.00 g, 8.14 mmol) and copper (I) cyanide (7.29 g, 81.0 mmol) was added N-methylpyrrolidinone (25 mL). This suspension under N2 was placed in an oil bath at 175° C. After 5 hours the reaction mixture was allowed to cool to room temperature. Glacial acetic acid (30 mL) was added to the mixture and stirred for 10 minutes. The mixture was diluted with ethyl acetate (100 mL), filtered through diatomaceous earth and the pad was washed with ethyl acetate (100 mL). The filtrate was washed with water (3×100 mL) and brine (2×100 mL). The organic fraction was dried (Na2SO4), filtered and the solvent was removed under reduced pressure to yield a solid. This was adsorbed onto silica gel and purified by column chromatography on a pre-packed silica gel Redi Sep 120 gram column, eluting with 0-5% methanol in CH2Cl2 to yield the title compound. 1H NMR (DMSO-d6) δ 12.70 (s, 1H), 7.76-7.72 (m, 1H), 7.62-7.56 (m, 2H), 7.54-7.52 (m, 1H), 6.48 (d, J=6.8 Hz, 1H). LRMS (M+1)=314.87.

Provenance & Evidence