3-(Trifluoromethyl)-2-pyridinecarbonitrile

Synthesis

65753-47-1

406933-21-9

The general procedure for the synthesis of 3-trifluoromethyl-2-pyridinecarbonitrile from 2-chloro-3-trifluoromethylpyridine was as follows: 2-chloro-3-trifluoromethylpyridine (5 g, 28.9 mmol) was dissolved in dimethylformamide (40 ml) under the protection of nitrogen, and zinc cyanide (2 g, 17.4 mmol), zinc powder (85 mg, 1.3 mmol) and 1,1'- diphenylphosphine ferrocene palladium(II) dichloride complex with dichloromethane (460 mg, 0.63 mmol). The reaction mixture was heated to reflux and kept for 4 hours. After completion of the reaction, it was cooled to room temperature, diluted with ethyl acetate and washed with saturated saline. The aqueous phase was back-extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by fast column chromatography (eluent: hexane solution of 20% ethyl acetate) afforded 3-trifluoromethyl-2-pyridinecarbonitrile (4.67 g, 98% yield) as a yellow oil.1H NMR (400 MHz, CDCl3) δ 8.59 (1H, dd, J=4.4,1.2 Hz), 8.05-8.02 (1H, m), 7.40- 7.37 (1H, m) ppm.

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