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

HRID 1963480Notes

Reaction equation

HRID 1963480 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]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730432HCID 131730432, compound

Product 1

HCID 667321785-(trans-2-(2-Fluoro-4-(trifluoromethyl)phenyl)-piperidin-4-yl)isoxazol-3(2h)-oneYield 43%

Procedure

Trans-methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (400 mg, 1.03 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 8.12 mL, 46.35 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-(trans-2-(2-fluoro-4-(trifluoromethyl)phenyl)-piperidin-4-yl)isoxazol-3(2H)-one (146 mg, 43%). 1H NMR (600 MHz, dmso) δ 1.63-1.71 (m, 1H), 1.78-1.86 (m, 1H), 1.91-1.99 (m, 1H), 2.04-2.11 (m, 1H), 2.69 (dt, 1H), 2.87-2.93 (m, 1H), 3.19-3.23 (m, 1H), 4.00 (d, 1H), 5.88 (d, 1H), 7.53-7.61 (m, 2H), 7.77 (t, 1H). HRMS Calculated for [C15H14F4N2O2+H]+: 331.1070. Found: 331.1074

Workup

  1. customThe solvent was evaporated
  2. 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-cd3af3b3a72d4a37bfd24431d997cc90
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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