Hydrogen Bromide → 5-((2R,4S)-2-(2-fluoro-4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C@H:12]1[CH2:17][C@@H:16]([C:18]2[O:22][NH:21][C:20](=[O:23])[CH:19]=2)[CH2:15][CH2:14][N:13]1C(OC)=O.Br>>[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:5]=[CH:4][C:3]=1[C@H:12]1[CH2:17][C@@H:16]([C:18]2[O:22][NH:21][C:20](=[O:23])[CH:19]=2)[CH2:15][CH2:14][NH:13]1Participants
Procedure
(2R,4S)-Methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.96 g, 2.47 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 19.48 mL, 111.25 mmol) and the mixture was 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-(2-fluoro-4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (687 mg, 84%). 1H NMR (600 MHz, dmso) δ 1.36 (q, 1H), 1.48 (dq, 1H), 1.84-1.92 (m, 1H), 1.94-2.02 (m, 1H), 2.75 (dt, 1H), 2.92 (tt, 1H), 3.08-3.15 (m, 1H), 4.00 (d, 1H), 5.73 (s, 1H), 7.53-7.62 (m, 2H), 7.78 (t, 1H). HRMS Calculated for [C15H14F4N2O2+H]+: 331.1070. Found: 331.1086
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-bb803e2dbcf0438c84693bd8f9ae8d21
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415378B2
Reaction notes
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