Hydrogen Bromide → 5-(trans-2-(3,4-Difluorophenyl)piperidin-4-yl)isoxazol-3(2h)-one

HRID 1963362Notes

Reaction equation

HRID 1963362 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:14][C@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][N:10]2C(OC)=O)[CH:5]=[CH:6][C:7]=1[F:8].Br>>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:14][C@H:13]([C:15]3[O:19][NH:18][C:17](=[O:20])[CH:16]=3)[CH2:12][CH2:11][NH:10]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730380trans-Methyl 2-(3,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667323985-(trans-2-(3,4-Difluorophenyl)piperidin-4-yl)isoxazol-3(2h)-oneYield 68%

Procedure

Trans-methyl 2-(3,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (242 mg, 0.72 mmol) was dissolved in hydrobromic acid (33% in AcOH, 4 mL, 24.31 mmol) and stirred at room temperature for 20 h. The solvent was evaporated in vacuo. The residue was purified by preparative HPLC (Instrument: Agilent, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-(trans-2-(3,4-difluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (137 mg, 68%). 1H NMR (600 MHz, dmso) δ 1.74-1.81 (m, 2H), 1.84-1.89 (m, 1H), 1.98-2.03 (m, 1H), 2.65-2.71 (m, 1H), 2.81 (dt, 1H), 3.09-3.13 (m, 1H), 3.70 (dd, 1H), 5.96 (s, 1H), 7.18-7.22 (m, 1H), 7.30-7.36 (m, 1H), 7.39-7.44 (m, 1H). HRMS Calcd for [C14H14F2N2O2+H]+: 281.1101. Found: 281.1114.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customThe residue was purified by preparative HPLC (Instrument: Agilent, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm)

Sources & evidence

ORD record
ord-a7fa8fde9a3e4aa4944320314ec03fc6
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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