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

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Reaction Steps

(2R,4S)-Methyl 2-(3-tert-butylphenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.340 g, 0.95 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 5.49 mL, 31.35 mmol) and the solution 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-(3-tert-butylphenyl)piperidin-4-yl)isoxazol-3(2H)-one (107 mg, 37%). 1H NMR (400 MHz, dmso) δ 1.26 (s, 9H), 1.32-1.43 (m, 1H), 1.43-1.54 (m, 1H), 1.81-1.90 (m, 1H), 1.90-1.99 (m, 1H), 2.68-2.78 (m, 1H), 2.80-2.91 (m, 1H), 3.08-3.16 (m, 1H), 3.59-3.66 (m, 1H), 5.72 (s, 1H), 7.13-7.29 (m, 3H), 7.37 (s, 1H). HRMS Calcd for [C18H24N2O2+H]+: 301.1916. Found: 301.1909.

Provenance & Evidence