反应详情

(2R,4R)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (185 mg, 0.55 mmol) (from example 102, step 2) was stirred in hydrogen bromide (33% in AcOH) overnight (17 h). Evaporation of solvents and purification by preparative HPLC (Instrument: FractionLynx I, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) yielded 5-((2R,4R)-2-(2-fluorobenzyl)-piperidin-4-yl)isoxazol-3(2H)-one (75 mg, 49%). 1H NMR (600 MHz, DMSO) δ 1.48-1.55 (m, 1H), 1.68-1.80 (m, 3H), 2.58-2.64 (m, 1H), 2.72 (d, 2H), 2.81-2.87 (m, 1H), 2.87-2.94 (m, 1H), 3.12-3.17 (m, 1H), 5.70 (s, 1H), 7.11-7.17 (m, 2H), 7.24-7.31 (m, 2H). HRMS Calcd for [C15H17FN2O2+H]+: 277.1352. Found: 277.1357.

1. customEvaporation of solvents and purification by preparative HPLC (Instrument: FractionLynx I, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm)