trans-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate → 5-(trans-2-(3-(Trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2h)-one
Reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([C@@H:7]2[CH2:12][CH2:11][N:10](C(OC)=O)[C@@H:9]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[CH2:8]2)[O:4][NH:3]1>Br>[F:26][C:24]([F:25])([F:27])[C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=1)[CH2:17][C@H:9]1[CH2:8][C@H:7]([C:5]2[O:4][NH:3][C:2](=[O:1])[CH:6]=2)[CH2:12][CH2:11][NH:10]1Participants
Procedure
Hydrogen bromide (33% in acetic acid, 10 mL) was added to a reaction flask containing trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)benzyl)piperidine-1-carboxylate (0.25 g, 0.65 mmol). The reaction was stirred vigorously 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-(trans-2-(3-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (91 mg, 43%). 1H NMR (600 MHz, cd3od) δ 1.94-2.05 (m, 1H), 2.11-2.30 (m, 3H), 3.09-3.26 (m, 3H), 3.37-3.47 (m, 2H), 3.58-3.66 (m, 1H), 5.83 (s, 1H), 7.53-7.67 (m, 4H). HRMS Calculated for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1322
Workup
- customThe solvent was evaporated
- customthe 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)
Sources & evidence
- ORD record
- ord-599ca6858b2d44e7a167c84656f84a8f
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415378B2
Reaction notes
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