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

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Reaction Steps

(2R,4R)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (32.5 mg, 0.09 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 0.8 mL, 4.57 mmol) and the mixture stirred at room temperature overnight. 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,4R)-2-(3,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (10.4 mg, 38%). 1H NMR (600 MHz, cd3od) δ 1.71-1.78 (m, 1H), 1.96-2.04 (m, 1H), 2.05-2.12 (m, 2H), 2.80-2.92 (m, 2H), 2.96-3.03 (m, 1H), 3.15-3.25 (m, 2H), 3.26-3.35 (m, 1H), 5.50 (s, 1H), 6.99-7.05 (m, 1H), 7.13-7.23 (m, 2H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1267

Provenance & Evidence