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

HRID 1963552Notes

Reaction equation

HRID 1963552 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 68503458(2R,4S)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469377045-((2R,4S)-2-(2-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 124.1%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

(2R,4S)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (492 mg, 1.47 mmol) was stirred in hydrogen bromide (33% in AcOH) overnight (19 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-((2R,4S)-2-(2-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (504 mg, 124%). The sample contained DMSO and acetic acid. 1H NMR (400 MHz, cd3od) δ 1.50-1.65 (m, 1H), 1.69-1.84 (m, 1H), 2.08-2.22 (m, 2H), 2.89-3.18 (m, 4H), 3.38-3.51 (m, 2H), 5.66 (s, 1H), 7.11-7.23 (m, 2H), 7.28-7.41 (m, 2H). HRMS Calcd for [C15H17FN2O2+H]+: 277.1352. Found: 277.1344.

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-926921841ab94393a31478c98cb8a56b
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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