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

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Reaction Steps

Trans-methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (400 mg, 1.03 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 8.12 mL, 46.35 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated 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-(trifluoromethyl)phenyl)-piperidin-4-yl)isoxazol-3(2H)-one (146 mg, 43%). 1H NMR (600 MHz, dmso) δ 1.63-1.71 (m, 1H), 1.78-1.86 (m, 1H), 1.91-1.99 (m, 1H), 2.04-2.11 (m, 1H), 2.69 (dt, 1H), 2.87-2.93 (m, 1H), 3.19-3.23 (m, 1H), 4.00 (d, 1H), 5.88 (d, 1H), 7.53-7.61 (m, 2H), 7.77 (t, 1H). HRMS Calculated for [C15H14F4N2O2+H]+: 331.1070. Found: 331.1074

Provenance & Evidence