Hydrogen Bromide → 5-((2S,4S)-2-(3,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one

HRID 1963602Notes

Reaction equation

HRID 1963602 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[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[F:25])[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

3

Reactant 2

HCID 260Hydrogen Bromide2×HCID 68501682(2S,4S)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667323045-((2S,4S)-2-(3,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 22.2%

Procedure

(2S,4S)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (45 mg, 0.13 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 1 mL, 5.71 mmol) and the mixture stirred at room temperature. After 17 h more hydrogen bromide (33% in acetic acid, 0.5 mL, 2.85 mmol) was added and the reaction continued at room temperature for a total of 24 h. The solvent was 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-((2S,4S)-2-(3,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (8.5 mg, 22%). 1H NMR (600 MHz, cd3od) δ 1.71-1.79 (m, 1H), 1.96-2.04 (m, 1H), 2.04-2.12 (m, 2H), 2.79-2.92 (m, 2H), 2.95-3.03 (m, 1H), 3.14-3.36 (m, 3H), 5.51 (s, 1H), 7.00-7.04 (m, 1H), 7.13-7.24 (m, 2H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1276

Workup

  1. customcontinued at room temperature for a total of 24 h
  2. customThe solvent was evaporated
  3. 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-137a593617c041078a7621a876da8146
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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