Hydrogen Bromide → 5-(trans-2-(2-Fluoro-4-(trifluoromethoxy)phenyl)-piperidin-4-yl)isoxazol-3(2h)-one

HRID 1963443Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[C@H:13]1[CH2:18][C@H:17]([C:19]2[O:23][NH:22][C:21](=[O:24])[CH:20]=2)[CH2:16][CH2:15][N:14]1C(OC)=O.Br>>[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:10])([F:11])[F:12])[CH:5]=[CH:4][C:3]=1[C@H:13]1[CH2:18][C@H:17]([C:19]2[O:23][NH:22][C:21](=[O:24])[CH:20]=2)[CH2:16][CH2:15][NH:14]1

Participants

Reactant 2

HCID 260Hydrogen Bromide

HCID 131730415HCID 131730415, compound

Product 1

HCID 667324815-(trans-2-(2-Fluoro-4-(trifluoromethoxy)phenyl)-piperidin-4-yl)isoxazol-3(2h)-oneYield 59.4%

Procedure

Trans-methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (365 mg, 0.90 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 7.115 mL, 40.62 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-(trans-2-(2-fluoro-4-(trifluoromethoxy)phenyl)-piperidin-4-yl)isoxazol-3(2H)-one (185 mg, 59%). 1H NMR (600 MHz, dmso) δ 1.64-1.72 (m, 1H), 1.77-1.85 (m, 1H), 1.91-1.97 (m, 1H), 2.02-2.08 (m, 1H), 2.69 (dt, 1H), 2.86-2.92 (m, 1H), 3.17-3.22 (m, 1H), 3.95 (dd, 1H), 5.87 (d, 1H), 7.19-7.23 (m, 1H), 7.28-7.32 (m, 1H), 7.66 (t, 1H); HRMS Calculated for [C15H14F4N2O3+H]+: 347.1019. Found: 347.1002

Workup

customThe solvent was removed in vacuo
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-d4a5c8141e6743ee8a75e582b286ec29
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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