Hydrogen Bromide → 5-(trans-2-(3,5-Difluoro-4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2h)-one
Reaktionsgleichung
[F:1][C:2]1[CH:3]=[C:4]([C@H:13]2[CH2:18][C@H:17]([C:19]3[O:23][NH:22][C:21](=[O:24])[CH:20]=3)[CH2:16][CH2:15][N:14]2C(OC)=O)[CH:5]=[C:6]([F:12])[C:7]=1[C:8]([F:11])([F:10])[F:9].Br>>[F:12][C:6]1[CH:5]=[C:4]([C@H:13]2[CH2:18][C@H:17]([C:19]3[O:23][NH:22][C:21](=[O:24])[CH:20]=3)[CH2:16][CH2:15][NH:14]2)[CH:3]=[C:2]([F:1])[C:7]=1[C:8]([F:9])([F:10])[F:11]Komponenten
3
Versuchsvorschrift
Trans-methyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (26 mg, 0.06 mmol) was dissolved in hydrogen bromide (33% in AcOH, 2 mL, 0.06 mmol) and stirred at room temperature for 20 h. 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-(3,5-difluoro-4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (7.00 mg, 31%). 1H NMR (600 MHz, dmso) δ 1.73-1.88 (m, 3H), 2.02-2.08 (m, 1H), 2.64-2.70 (m, 1H), 2.77-2.83 (m, 1H), 3.06-3.11 (m, 1H), 3.83-3.86 (m, 1H), 6.02 (s, 1H), 7.42 (d, 2H). HRMS Calcd for [C15H13F5N2O2+H]+: 349.0975. Found: 349.0983.