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

HRID 1963540Notes

Reaction equation

HRID 1963540 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 BromideHCID 68504226(2R,4S)-Methyl 2-(4-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469377015-((2R,4S)-2-(4-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 67.2%

Procedure

(2R,4S)-Methyl 2-(4-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (647 mg, 1.94 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 15 mL, 85.65 mmol) and the mixture 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-((2R,4S)-2-(4-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (360 mg, 67%). 1H NMR (600 MHz, DMSO) δ 1.08 (q, 1H), 1.37 (dq, 1H), 1.73-1.81 (m, 2H), 2.44-2.73 (m, 5H), 2.96-3.03 (m, 1H), 5.70 (s, 1H), 7.07-7.14 (m, 2H), 7.21-7.27 (m, 2H). HRMS Calculated for [C15H17FN2O2+H]+: 277.1352. Found: 277.1333

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-1c9db5032c804fd5b44c9ec7d4b6eb0f
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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