Hydrogen Bromide → HCID 66732108, compound

HRID 1963638Notes

Reaction equation

HRID 1963638 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[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]=[C:23]([C:25]([F:27])([F:26])[F:28])[CH:24]=1)[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 131730495HCID 131730495, compound

Product 1

HCID 66732108HCID 66732108, compoundYield 79.3%

Procedure

Trans-methyl 2-(3-fluoro-5-(trifluoromethyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.255 g, 0.63 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 5 mL, 71.37 mmol) and stirred at room temperature for 1 week. The solvents were 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-(trans-2-(3-fluoro-5-(trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (172 mg, 79%). 1H NMR (600 MHz, dmso) δ 1.43-1.51 (m, 1H), 1.62-1.80 (m, 3H), 2.51-2.58 (m, 1H), 2.71-2.82 (m, 3H), 2.86-2.94 (m, 1H), 3.07-3.14 (m, 1H), 5.72 (s, 1H), 7.37-7.46 (m, 3H). HRMS Calculated for [C16H16F4N2O2+H]+: 345.1226. Found: 345.1241

Workup

  1. customThe solvents were 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-c465f489e7f84f4b8cfdef8497a9b069
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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