4-(Trifluoromethyl)aniline → 1-Boc-4-(4-Trifluoromethyl-phenylamino)-piperidine

Participants

Reaction Steps

A solution of 4-(trifluoromethyl)aniline (0.772 mL, 6.21 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (2.47 g, 12.4 mmol) in acetic acid (30 mL) was treated with anhydrous Na2SO4 powder (8.82 g, 62.1 mmol). The mixture was stirred at ambient temperature for 20 minutes, and then sodium triacetoxyborohydride (3.95 g, 18.6 mmol) was added in approximately 5 equal portions over 2 minutes. The reaction was allowed to proceed at ambient temperature for 3 hours. The reaction mixture was carefully poured into a well-stirred mixture of 1:1 ethyl acetate/hexanes (100 mL) and saturated NaHCO3 solution (150 mL), and then basified with excess 2 N aqueous NaOH solution. The phases were separated, and the organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was triturated with hexanes and the solid was collected by vacuum filtration and air-dried to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.35 (d, J=8.6, 2H), 6.69 (d, J=8.6, 2H), 6.25 (d, J=8.0, 1H), 3.95-3.80 (m, 2H), 3.56-3.40 (m, 1H), 3.02-2.81 (m, 2H), 1.94-1.80 (m, 2H), 1.40 (s, 9H), 1.33-1.18 (m, 2H); MS (DCI+) m/z 345 (M+H)+.

Provenance & Evidence