反应详情

Trans-methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.25 g, 0.71 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 6.21 mL, 35.48 mmol) and stirred at room temperature for 16 h. The solvents were evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-(trans-2-(2,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (94.6 mg, 45%). 1H NMR (600 MHz, dmso) δ 1.43-1.51 (m, 1H), 1.63-1.78 (m, 3H), 2.52-2.60 (m, 1H), 2.65 (d, 2H), 2.76-2.87 (m, 2H), 3.08-3.13 (m, 1H), 5.67 (s, 1H), 6.98 (td, 1H), 7.12 (td, 1H), 7.27-7.34 (m, 1H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1265

1. customThe solvents were evaporated
2. customthe residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm)