Acetic Acid → 5-((2R,4S)-2-(2,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one

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Reaction Steps

(2R,4S)-Methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (399 mg, 1.13 mmol) was dissolved in hydrogen bromide (33% in acetic acid (8.2 mL, 46.87 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo and the residue purified by preparative HPLC (Instrument: FractionLynx III, 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-(2,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (146 mg, 44%). 1H NMR (400 MHz, cd3od) δ 1.43 (q, 1H), 1.67 (dq, 1H), 1.99-2.12 (m, 2H), 2.79-2.97 (m, 4H), 3.14-3.24 (m, 1H), 3.27-3.35 (m, 1H), 5.52 (s, 1H), 6.91-7.02 (m, 2H), 7.27-7.36 (m, 1H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1252

Provenance & Evidence