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

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Reaction Steps

(2R,4S)-Methyl 2-(4-chloro-2-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.504 g, 1.42 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 11.20 mL, 63.93 mmol) and the mixture was stirred at room temperature overnight. The solvent was 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-((2R,4S)-2-(4-chloro-2-fluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (313 mg, 74%). 1H NMR (600 MHz, dmso) δ 1.35 (q, 1H), 1.46 (dq, 1H), 1.86 (d, 1H), 1.94 (d, 1H), 2.73 (dt, 1H), 2.90 (tt, 1H), 3.10 (td, 1H), 3.91 (d, 1H), 5.73 (s, 1H), 7.25 (dd, 1H), 7.34 (dd, 1H), 7.55 (t, 1H). HRMS Calcd for [C14H14ClFN2O2+H]+: 297.0806. Found: 297.0786.

Provenance & Evidence