Hydrogen Bromide → 5-(trans-2-(2,6-Difluorobenzyl)piperidin-4-yl)isoxazol-3(2h)-one

HRID 1963616Notes

Reaction equation

HRID 1963616 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:3]=1[CH2:4][C@H:5]1[CH2:10][C@H:9]([C:11]2[O:15][NH:14][C:13](=[O:16])[CH:12]=2)[CH2:8][CH2:7][N:6]1C(OC)=O.Br>>[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:3]=1[CH2:4][C@H:5]1[CH2:10][C@H:9]([C:11]2[O:15][NH:14][C:13](=[O:16])[CH:12]=2)[CH2:8][CH2:7][NH:6]1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730487trans-Methyl 2-(2,6-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667318995-(trans-2-(2,6-Difluorobenzyl)piperidin-4-yl)isoxazol-3(2h)-oneYield 1.7%

Procedure

Trans-methyl 2-(2,6-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.329 g, 0.93 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 7.5 mL, 42.82 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-(2,6-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (4.6 mg, 1.7%). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1257

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-4be4884638e34403a240ca1ddae85fc1
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…