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

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Reaction Steps

(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate (0.64 g, 1.67 mmol) (from example 107, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 5 mL, 71.37 mmol) and stirred at room temperature for 41 h. Reaction mixture was evaporated and restarted under the same conditions. After 28 h solvents evaporated and the residue purified 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) to yield 5-((2S,4R)-2-(3-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (368 mg, 68%). 1H NMR (600 MHz, DMSO) δ 1.07-1.15 (m, 1H), 1.36 (dq, 1H), 1.74-1.80 (m, 2H), 2.54-2.58 (m, 1H), 2.64-2.79 (m, 4H), 2.96-3.01 (m, 1H), 5.66 (s, 1H), 7.50-7.59 (m, 4H). HRMS Calculated for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1333

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