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

HRID 1963387Notes

Reaction equation

HRID 1963387 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([C@@H:7]2[CH2:12][CH2:11][N:10](C(OC)=O)[C@@H:9]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:26][C:23]([F:24])([F:25])[C:20]1[CH:19]=[CH:18][C:17]([C@H:9]2[CH2:8][C@H:7]([C:5]3[O:4][NH:3][C:2](=[O:1])[CH:6]=3)[CH2:12][CH2:11][NH:10]2)=[CH:22][CH:21]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 131730392trans-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate

Product 1

HCID 667316165-(trans-2-(4-(Trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2h)-oneYield 40%

Procedure

Trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (148 mg, 0.40 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 3 mL, 17.13 mmol) and the solution stirred at room temperature overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-(trans-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (50 mg, 40%). 1H NMR (600 MHz, dmso) δ 1.75-1.83 (m, 2H), 1.84-1.92 (m, 1H), 2.00-2.06 (m, 1H), 2.70 (dt, 1H), 2.79-2.86 (m, 1H), 3.09-3.15 (m, 1H), 3.77 (d, 1H), 5.95 (s, 1H), 7.59 (d, 2H), 7.64 (d, 2H). HRMS Calculated for [C15H15F3N2O2+H]+: 313.1164. Found: 313.1166

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by preparative HPLC (Instrument: FractionLynx II, 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-9496450e0d374f639a31977ac09aea65
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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