Hydrogen Bromide → 5-((2R,4S)-2-(2,6-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one

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Reaction Steps

(2R,4S)-methyl 2-(2,6-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (370 mg, 1.05 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 8 mL, 45.68 mmol) and the mixture stirred at room temperature for 24 h. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx III, 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-(2,6-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (254 mg, 82%). 1H NMR (600 MHz, cd3od) δ 1.47 (q, 1H), 1.67 (qd, 1H), 2.02 (dd, 2H), 2.78-3.02 (m, 4H), 3.16-3.24 (m, 1H), 3.27-3.33 (m, 1H), 5.49 (s, 1H), 6.98 (t, 2H), 7.27-7.37 (m, 1H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1248

Provenance & Evidence