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

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Reaction Steps

(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (259 mg, 0.73 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 4 mL, 22.84 mmol) and the mixture 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-(2,4,5-trifluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (161 mg, 74%). 1H NMR (600 MHz, dmso) δ 1.36 (q, 1H), 1.45 (dq, 1H), 1.83-1.90 (m, 1H), 1.91-1.97 (m, 1H), 2.74 (dt, 1H), 2.90 (tt, 1H), 3.06-3.13 (m, 1H), 3.91 (d, 1H), 5.74 (d, 1H), 7.44-7.57 (m, 2H). HRMS Calculated for [C14H13F3N2O2+H]+: 299.1007. Found: 299.1021

Provenance & Evidence