Hydrogen Bromide → 5-(trans-2-(2-Fluoro-4-(trifluoromethoxy)phenyl)-piperidin-4-yl)isoxazol-3(2h)-one

Participants

Reaction Steps

Trans-methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (365 mg, 0.90 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 7.115 mL, 40.62 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo and the residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-(trans-2-(2-fluoro-4-(trifluoromethoxy)phenyl)-piperidin-4-yl)isoxazol-3(2H)-one (185 mg, 59%). 1H NMR (600 MHz, dmso) δ 1.64-1.72 (m, 1H), 1.77-1.85 (m, 1H), 1.91-1.97 (m, 1H), 2.02-2.08 (m, 1H), 2.69 (dt, 1H), 2.86-2.92 (m, 1H), 3.17-3.22 (m, 1H), 3.95 (dd, 1H), 5.87 (d, 1H), 7.19-7.23 (m, 1H), 7.28-7.32 (m, 1H), 7.66 (t, 1H); HRMS Calculated for [C15H14F4N2O3+H]+: 347.1019. Found: 347.1002

Provenance & Evidence