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

HRID 1963645Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[C:25]([F:28])([F:27])[F:26])[CH2:5][C@H:6]1[CH2:11][C@H:10]([C:12]2[O:16][NH:15][C:14](=[O:17])[CH:13]=2)[CH2:9][CH2:8][N:7]1C(OC)=O.Br>>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[C:25]([F:27])([F:26])[F:28])[CH2:5][C@H:6]1[CH2:11][C@H:10]([C:12]2[O:16][NH:15][C:14](=[O:17])[CH:13]=2)[CH2:9][CH2:8][NH:7]1

Participants

Reactant 2

HCID 260Hydrogen Bromide

HCID 131730498HCID 131730498, compound

Product 1

HCID 667323875-(trans-2-(3-Fluoro-4-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2h)-oneYield 83%

Procedure

Trans-methyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (0.224 g, 0.56 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 5 mL, 71.37 mmol) and stirred at room temperature for 1 week. The solvents were evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx III, 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-fluoro-4-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (160 mg, 83%). 1H NMR (600 MHz, dmso) δ 1.48 (ddd, 1H), 1.63-1.81 (m, 3H), 2.51-2.59 (m, 1H), 2.70-2.82 (m, 3H), 2.88-2.95 (m, 1H), 3.07-3.14 (m, 1H), 5.72 (s, 1H), 7.21 (d, 1H), 7.33 (d, 1H), 7.63 (t, 1H). HRMS Calculated for [C16H16F4N2O2+H]+: 345.1226. Found: 345.1241

Workup

customThe solvents were evaporated
customthe residue purified by preparative HPLC (Instrument: FractionLynx III, 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-20050ef63f334c7e982f5df04aae4d59
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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