Hydrogen Bromide → HCID 46938213, compound

HRID 1963378Notes

Reaction equation

HRID 1963378 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][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=3)[CH2:8]2)[O:4][NH:3]1.Br>>[F:25][C:23]([F:24])([F:26])[C:19]1[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][CH:20]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66734640HCID 66734640, compound

Product 1

HCID 46938213HCID 46938213, compoundYield 22%

Procedure

(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3-(trifluoromethyl)phenyl)piperidine-1-carboxylate (0.152 g, 0.42 mmol) (from example 30, step 3) was dissolved in hydrogen bromide (33% in acetic acid, 3.30 mL, 18.83 mmol) and the mixture was 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-((2S,4R)-2-(3-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (28 mg, 22%). 1H NMR (600 MHz, dmso) δ 1.35 (q, 1H), 1.47 (qd, 1H), 1.87 (d, 1H), 2.00 (d, 1H), 2.73 (dt, 1H), 2.84-2.91 (m, 1H), 3.09-3.14 (m, 1H), 3.75 (d, 1H), 5.74 (s, 1H), 7.50-7.54 (m, 1H), 7.55-7.58 (m, 1H), 7.66 (d, 1H), 7.71 (s, 1H). HRMS Calculated for [C15H15F3N2O2+H]+: 313.1164. Found: 313.1158

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-05aabd484455430888a6890eeae7a610
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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