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

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Reaction Steps

(2R,4S)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (550 mg, 1.56 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 15 mL, 85.65 mmol) and the mixture stirred at room temperature overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx I, 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-(3,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (183 mg, 40%). 1H NMR (600 MHz, cd3od) δ 1.41 (q, 1H), 1.67 (dq, 1H), 1.99-2.08 (m, 2H), 2.77-2.95 (m, 4H), 3.17-3.24 (m, 1H), 3.26-3.34 (m, 1H), 5.49 (s, 1H), 7.00-7.05 (m, 1H), 7.14-7.22 (m, 2H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1253

Provenance & Evidence