(2S,4S)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate → 5-((2S,4S)-2-(2-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one

HRID 1963555Notes

Reaction equation

HRID 1963555 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[CH:21][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]=[CH:21][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 1

HCID 66732457(2S,4S)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469377055-((2S,4S)-2-(2-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 70%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

(2S,4S)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (199 mg, 0.60 mmol) was stirred in hydrogen bromide (33% in AcOH) overnight (17 h). Evaporation of solvents and purification by preparative HPLC (Instrument: FractionLynx I, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) yielded 5-((2S,4S)-2-(2-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (115 mg, 70%). 1H NMR (600 MHz, DMSO) δ 1.47-1.56 (m, 1H), 1.67-1.81 (m, 3H), 2.57-2.64 (m, 1H), 2.72 (d, 2H), 2.81-2.87 (m, 1H), 2.87-2.95 (m, 1H), 3.12-3.18 (m, 1H), 5.70 (s, 1H), 7.09-7.18 (m, 2H), 7.22-7.33 (m, 2H). HRMS Calcd for [C15H17FN2O2+H]+: 277.1352. Found: 277.1352.

Workup

  1. customEvaporation of solvents and purification by preparative HPLC (Instrument: FractionLynx I, 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-133dd9e1d01b4dfc97f7bb6c0aaf43ee
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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