N-(2-AMINO-4-TRIFLUOROMETHYLPHENYL)PIPERIDINE

1692-79-1

1496-40-8

To a solution of methanol (10 ml) containing 1-(2-nitro-4-(trifluoromethyl)phenyl)piperidine (559 mg, 2.03 mmol) was sequentially added concentrated hydrochloric acid (2.00 ml, 24.0 mmol) and anhydrous stannous dichloride (2.50 g, 13.1 mmol) at 0 °C. The reaction mixture was gradually warmed up to room temperature with continuous stirring for 17.5 hours. Upon completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the mixture for neutralization. Subsequently, the mixture was extracted three times with ethyl acetate. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50 g silica gel, eluent hexane/ethyl acetate = 14/1) to afford 2-piperidin-1-yl-5-(trifluoromethyl)aniline (448 mg, 1.83 mmol, 90.4% yield) as a light yellow solid. The product was characterized by TLC and 1H NMR (CDCl3, 400 MHz): TLC Rf 0.30 (unfolding agent hexane/acetone=18/1); 1H NMR (CDCl3, 400 MHz) δ 1.59-1.60 (m, 2H, CH2), 1.71 (tt, 4H, J=5.4,5.4Hz, 2CH2), 2.85 ( brs, 4H, 2CH2), 4.09 (brs, 2H, NH2), 6.92 (d, 1H, J=1.9Hz, aromatic-H), 6.97 (dd, 1H, J=1.9,8.4Hz, aromatic-H), 7.01 (d, 1H, J=8.4Hz, aromatic-H).