Hydrogen Bromide → 5-((2R,4S)-2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidin-4-yl)isoxazol-3(2H)-one

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Reaction Steps

(2R,4S)-Methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (458 mg, 1.13 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 8.93 mL, 50.98 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo 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-((2R,4S)-2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (246 mg, 63%). 1H NMR (600 MHz, dmso) δ 1.37 (q, 1H), 1.47 (dq, 1H), 1.84-1.90 (m, 1H), 1.93-1.99 (m, 1H), 2.74 (dt, 1H), 2.87-2.94 (m, 1H), 3.07-3.13 (m, 1H), 3.94 (dd, 1H), 5.74 (s, 1H), 7.18-7.22 (m, 1H), 7.28-7.33 (m, 1H), 7.66 (t, 1H); HRMS Calculated for [C15H14F4N2O3+H]+: 347.1019. Found: 347.0995

Provenance & Evidence