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

HRID 1963385Notes

Reaction equation

HRID 1963385 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 Bromide2×HCID 66735438(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate

Product 1

HCID 469382165-((2S,4R)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 67.4%

Procedure

(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (591 mg, 1.60 mmol) (from example 33, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 12 mL, 68.52 mmol) and the mixture stirred at room temperature. After 24 h more hydrogen bromide (33% in acetic acid, 5 mL, 28.55 mmol) was added and the reaction continued at room temperature for a total of 1.5 days. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx III, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-((2S,4R)-2-(4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (337 mg, 67%). 1H NMR (600 MHz, cd3od) δ 1.69-1.78 (m, 2H), 2.09 (d, 1H), 2.21 (d, 1H), 2.99-3.09 (m, 2H), 3.32-3.38 (m, 1H), 4.01-4.04 (m, 1H), 5.63 (s, 1H), 7.59 (d, 2H), 7.66 (d, 2H). HRMS Calculated for [C15H15F3N2O2+H]+: 313.1164. Found: 313.1156

Workup

  1. customcontinued at room temperature for a total of 1.5 days
  2. customThe solvent was evaporated
  3. customthe residue purified by preparative HPLC (Instrument: FractionLynx III, 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-c0714452658c4520813ad64c45462c80
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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