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

HRID 1963643Notes

Reaction equation

HRID 1963643 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[C:25]([F:28])([F:27])[F:26])[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][C:24]=1[C:25]([F:27])([F:26])[F:28])[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 66732432(2S,4R)-Methyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 667320815-((2S,4R)-2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-oneYield 65.4%

Procedure

(2S,4R)-Methyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (589 mg, 1.46 mmol) (from example 140, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 10 mL, 57.10 mmol) and the mixture stirred at room temperature overnight. The solvent was evaporated 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-((2S,4R)-2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (329 mg, 65%). 1H NMR (600 MHz, cd3od) δ 1.66 (q, 1H), 1.81 (dq, 1H), 2.17-2.25 (m, 2H), 3.00-3.15 (m, 4H), 3.47-3.52 (m, 1H), 3.56-3.62 (m, 1H), 5.76 (s, 1H), 7.28 (dd, 2H), 7.67 (t, 1H). HRMS Calculated for [C16H16F4N2O2+H]+: 345.1226. Found: 345.1225

Workup

  1. customThe solvent was evaporated
  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-06155bf4dbea403280a9f9db4cee1597
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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