Hydrogen Bromide → 5-((2R,4S)-2-(2,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one

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Reaction Steps

(2R,4S)-methyl 2-(2,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (187 mg, 0.55 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 4.36 mL, 24.87 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-((2R,4S)-2-(2,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (93 mg, 60%). 1H NMR (600 MHz, dmso) δ 1.36 (q, 1H), 1.46 (dq, 1H), 1.83-1.89 (m, 1H), 1.90-1.95 (m, 1H), 2.72 (dt, 1H), 2.89 (tt, 1H), 3.06-3.12 (m, 1H), 3.89 (dd, 1H), 5.73 (s, 1H), 7.03 (dt, 1H), 7.11-7.17 (m, 1H), 7.52-7.59 (m, 1H). HRMS Calculated for [C14H14F2N2O2+H]+: 281.1101. Found: 281.1106

Provenance & Evidence