反应详情

Trans-methyl 2-(3,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (242 mg, 0.72 mmol) was dissolved in hydrobromic acid (33% in AcOH, 4 mL, 24.31 mmol) and stirred at room temperature for 20 h. The solvent was evaporated in vacuo. The residue was purified by preparative HPLC (Instrument: Agilent, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-(trans-2-(3,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (137 mg, 68%). 1H NMR (600 MHz, dmso) δ 1.74-1.81 (m, 2H), 1.84-1.89 (m, 1H), 1.98-2.03 (m, 1H), 2.65-2.71 (m, 1H), 2.81 (dt, 1H), 3.09-3.13 (m, 1H), 3.70 (dd, 1H), 5.96 (s, 1H), 7.18-7.22 (m, 1H), 7.30-7.36 (m, 1H), 7.39-7.44 (m, 1H). HRMS Calcd for [C14H14F2N2O2+H]+: 281.1101. Found: 281.1114.

1. customThe solvent was evaporated in vacuo
2. customThe residue was purified by preparative HPLC (Instrument: Agilent, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm)