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

Participants

Reaction Steps

(2S,4R)-Methyl 2-(cyclohexyloxymethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (194 mg, 0.57 mmol) (from example 84, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 4.52 mL, 25.80 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-((2S,4R)-2-(Cyclohexyloxymethyl)piperidin-4-yl)isoxazol-3(2H)-one (4.5 mg, 3%). 1H NMR (600 MHz, dmso) δ 1.04-1.24 (m, 6H), 1.33-1.46 (m, 2H), 1.57-1.66 (m, 2H), 1.73-1.88 (m, 4H), 2.56-2.67 (m, 1H), 2.68-2.80 (m, 2H), 2.99-3.06 (m, 1H), 3.07-3.84 (m, 3H), 5.70 (s, 1H). HRMS Calculated for [C15H24N2O3+H]+: 281.1865. Found: 281.1893

Provenance & Evidence