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

HRID 1963543Notes

Reaction equation

HRID 1963543 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][C@@H:7]2[CH2:12][C@@H:11]([C:13]3[O:17][NH:16][C:15](=[O:18])[CH:14]=3)[CH2:10][CH2:9][N:8]2C(OC)=O)=[CH:4][CH:3]=1.Br>>[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][C@@H:7]2[CH2:12][C@@H:11]([C:13]3[O:17][NH:16][C:15](=[O:18])[CH:14]=3)[CH2:10][CH2:9][NH:8]2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 260Hydrogen Bromide3×HCID 66739000(2S,4S)-Methyl 2-(4-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469377025-((2S,4S)-2-(4-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 70,724.703%

Procedure

(2S,4S)-Methyl 2-(4-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (81 mg, 0.24 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 2 mL, 11.42 mmol) and the mixture stirred at room temperature for 24 h, then more hydrogen bromide (33% in acetic acid, 0.5 mL) was added and stirring continued overnight, then more hydrogen bromide (33% in acetic acid, 1 mL) was added and stirring continued overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: Agilent, 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-(4-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (46.9 g, 70%). 1H NMR (400 MHz, cd3od) δ 1.73-1.83 (m, 1H), 1.98-2.17 (m, 3H), 2.81-3.10 (m, 3H), 3.20-3.28 (m, 2H), 3.32-3.41 (m, 1H), 5.48 (d, 1H), 7.01-7.09 (m, 2H), 7.20-7.27 (m, 2H). HRMS Calculated for [C15H17FN2O2+H]+: 277.1352. Found: 277.1346

Workup

  1. stirringstirring continued overnight
  2. stirringstirring continued overnight
  3. customThe solvent was evaporated
  4. customthe residue purified by preparative HPLC (Instrument: Agilent, 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-064f0be24e8143c2984463f183c1aa0d
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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