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

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Reaction Steps

(2R,4S)-methyl 2-(3,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.7 g, 5.03 mmol) was dissolved in hydrobromic acid (33% in AcOH, 25 mL, 151.92 mmol) and stirred at room temperature for 20 h. The solvent was evaporated in vacuo. The compound was purified by preparative HPLC on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 5-30% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 25 minutes with a flow of 100 mL/min. The compound was repurified by preparative HPLC on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 0-30% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 25 minutes with a flow of 100 mL/min. 5-((2R,4S)-2-(3,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (0.923 g, 65.5%) was isolated as a white solid. 1H NMR (600 MHz, cd3od) δ 1.66-1.76 (m, 2H), 2.09 (d, 1H), 2.19 (d, 1H), 2.96-3.07 (m, 2H), 3.28-3.35 (omitted signals), 3.90-3.95 (m, 1H), 5.65 (s, 1H), 7.20-7.29 (m, 2H), 7.34-7.39 (m, 1H). HRMS Calcd for [C14H14F2N2O2+H]+: 281.1101. Found: 281.1106.

Provenance & Evidence