Piperazine → 1-[3-(Trifluoromethyl)pyridin-2-yl]piperazine

Participants

Reaction Steps

A solution of 2-chloro-3-trifluoromethylpyridine (6.57 g, 36.2 mmol) and piperazine (31.48 g, 365.5 mmol) in n-butanol was heated to 115° C. After 48 hours, the mixture was cooled to room temperature, the solvent removed under reduced pressure and the residue partitioned between water and ethyl acetate. The organic phase was dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (elution with 15% methanol:dichloromethane) to provide 3.35 g (40% yield) of the title compound as a tan solid. 1H NMR (300 MHz, DMSO-d6) δ 2.80 (m, 4H), 3.10 (m, 4H), 7.15 (ddd, 1H, J=7.8, 4.7, 1.0 Hz), 8.03 (dd, 1H, J=7.8, 1.7 Hz), 8.50 (ddd, 1H, J=4.8, 2.0, 0.7 Hz); MS (DCI/NH3) m/e 232 (M+H)+.

Provenance & Evidence