Acetic Acid → 5-((2R,4S)-2-(2,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one

HRID 1963628Notes

Reaction equation

HRID 1963628 reaction equation
[F:1][C:2]1[CH:24]=[C:23]([F:25])[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.C(O)(=O)C>Br>[F:1][C:2]1[CH:24]=[C:23]([F:25])[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

4

Reactant 2

HCID 176Acetic AcidHCID 68502687(2R,4S)-Methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667328105-((2R,4S)-2-(2,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 44%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

(2R,4S)-Methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (399 mg, 1.13 mmol) was dissolved in hydrogen bromide (33% in acetic acid (8.2 mL, 46.87 mmol) and stirred at room temperature for 16 h. The solvent was removed in vacuo and the residue purified by preparative HPLC (Instrument: FractionLynx III, 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-(2,4-difluorobenzyl)piperidin-4-yl)isoxazol-3(2H)-one (146 mg, 44%). 1H NMR (400 MHz, cd3od) δ 1.43 (q, 1H), 1.67 (dq, 1H), 1.99-2.12 (m, 2H), 2.79-2.97 (m, 4H), 3.14-3.24 (m, 1H), 3.27-3.35 (m, 1H), 5.52 (s, 1H), 6.91-7.02 (m, 2H), 7.27-7.36 (m, 1H). HRMS Calculated for [C15H16F2N2O2+H]+: 295.1258. Found: 295.1252

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by preparative HPLC (Instrument: FractionLynx III, 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-3a9fc2dfde104405b7edec43306a67f5
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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