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

HRID 1963546Notes

Reaction equation

HRID 1963546 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[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][CH:24]=1)[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 BromideHCID 68501479(2R,4S)-Methyl 2-(3-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667322025-((2R,4S)-2-(3-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 63.5%

Procedure

(2R,4S)-Methyl 2-(3-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (545 mg, 1.63 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 10 mL, 57.10 mmol) and the mixture stirred at room temperature for 23 h. The solvent was evaporated and the residue purified 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) to yield 5-((2R,4S)-2-(3-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (286 mg, 63.5%). 1H NMR (400 MHz, dmso) δ 1.09 (q, 1H), 1.36 (dq, 1H), 1.71-1.81 (m, 2H), 2.50-2.79 (m, 5H), 2.95-3.03 (m, 1H), 5.66 (s, 1H), 6.95-7.07 (m, 3H), 7.26-7.34 (m, 1H). HRMS Calculated for [C15H17FN2O2+H]+: 277.1352. Found: 277.1343

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified 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-d035061310ea4ccaa3b14670bc75e2d9
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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