反应详情

(2S,4R)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (596 mg, 1.69 mmol) (from example 120, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 15 mL, 85.65 mmol) and the mixture stirred at room temperature overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx I, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-((2S,4R)-2-(3,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (136 mg, 27%). 1H NMR (600 MHz, cd3od) δ 1.42 (q, 1H), 1.68 (dq, 1H), 2.04 (t, 2H), 2.78-2.95 (m, 4H), 3.19-3.25 (m, 1H), 3.29-3.35 (m, 1H), 5.49 (s, 1H), 7.00-7.05 (m, 1H), 7.14-7.22 (m, 2H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1264

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