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

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Reaction Steps

(2R,4S)-Methyl 2-(2-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (1.45 g, 3.77 mmol) was dissolved in hydrogen bromide (33% in HOAc, 19.82 mL, 113.18 mmol) and stirred overnight. The mixture was evaporated and purified on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-55% acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. 5-((2R,4S)-2-(2-Methyl-4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (810 mg, 65%) was isolated as a white powder. 1H NMR (400 MHz, cdcl3) δ 1.35 (q, 1H), 1.52 (dq, 1H), 1.88-2.01 (m, 2H), 2.42 (s, 3H), 2.75-2.85 (m, 1H), 2.89-3.00 (m, 1H), 3.12-3.18 (m, 1H), 3.93 (d, 1H), 5.76 (s, 1H), 7.49-7.54 (m, 2H), 7.73 (d, 1H). HRMS Calculated for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1312.

Provenance & Evidence