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

HRID 1963531Notes

Reaction equation

HRID 1963531 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][CH2:7][C@H:8]2[CH2:13][C@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2C(OC)=O)=[CH:4][CH:3]=1.Br>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C@H:8]2[CH2:13][C@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][NH:9]2)=[CH:24][CH:25]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730453trans-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667320165-(trans-2-(4-Fluorophenethyl)piperidin-4-yl)isoxazol-3(2h)-oneYield 70.7%

Procedure

Trans-methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (137 mg, 0.39 mmol) dissolved in hydrogen bromide (33% in acetic acid, 3.1 mL, 17.70 mmol) to give a yellow solution. The mixture was stirred at room temperature for 16 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-(4-fluorophenethyl)piperidin-4-yl)isoxazol-3(2H)-one (80 mg, 70%). 1H NMR (400 MHz, dmso) δ 1.42-1.78 (m, 5H), 1.82-1.95 (m, 1H), 2.52-2.68 (m, 4H), 2.74-2.84 (m, 1H), 3.05-3.13 (m, 1H), 5.73 (s, 1H), 7.01-7.10 (m, 2H), 7.15-7.25 (m, 2H). HRMS Calculated for [C16H19FN2O2+H]+: 291.1509. Found: 291.1522

Workup

  1. customto give a yellow solution
  2. customthe solvent was evaporated
  3. 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-7c13af0f5d1e4d969eb4bead1b77f0c8
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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