1-Hydroxybenzotriazole → 5-Phenyl-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenylamino)-piperidin-1-yl]-ethyl}-amide

Participants

Reaction Steps

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (0.0685 g, 0.00024 mol) in DMF (2 mL) was added DIPEA (0.173 g, 0.00134 mol), HOBt (0.045 g, 0.00034 mol) and EDCI.HCl (0.064 g, 0.00034 mol) at ambient temperature. After 2 minutes piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine dihydrochloride (0.068 g, 0.00024 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was collected and washed with brine solution, dried over sodium sulfate and concentrated. The resulting residue was purified by column chromatography using neutral aluminium oxide (35% ethyl acetate in hexane) to afford 0.0684 g (60%) of 5-phenyl-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenylamino)-piperidin-1-yl]-ethyl}-amide. LCMS: 473.17 (M+1)+, 97.41%, 1H NMR (DMSO-d6): δ 8.62 (t, 1H), 7.94 (m, 2H), 7.52 (m, 3H), 7.38 (m, 3H), 6.98 (d, 1H), 6.7 (t, 1H), 4.7 (d, 1H), 4.3 (d, 1H), 4.2 (d, 2H), 3.9 (d, 1H), 3.7 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 2.0 (m, 2H), 1.4 (m, 2H).

Provenance & Evidence