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

HRID 1963549Notes

Reaction equation

HRID 1963549 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 68498619(2S,4S)-methyl 2-(3-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 469377035-((2S,4S)-2-(3-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 81%

Procedure

(2S,4S)-methyl 2-(3-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (77 mg, 0.23 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 2 mL, 11.42 mmol) and the mixture stirred at room temperature 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-(3-fluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (51.4 mg, 81%). 1H NMR (400 MHz, cd3od) δ 1.74-1.84 (m, 1H), 1.98-2.16 (m, 3H), 2.84-3.10 (m, 3H), 3.19-3.29 (m, 2H), 3.35-3.44 (m, 1H), 5.50 (s, 1H), 6.96-7.07 (m, 3H), 7.29-7.37 (m, 1H). HRMS Calculated for [C15H17FN2O2+H]+: 277.1352. Found: 277.1357

Workup

  1. customThe solvent was evaporated
  2. 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-54ec50f572314245b89d922cd9f5b1a6
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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