Hydrogen Bromide → HCID 46937525, compound

HRID 1963465Notes

Reaction equation

HRID 1963465 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C@@H:12]2[CH2:17][C@H:16]([C:18]3[O:22][NH:21][C:20](=[O:23])[CH:19]=3)[CH2:15][CH2:14][N:13]2C(OC)=O)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].Br>>[CH3:1][C:2]1[CH:3]=[C:4]([C@@H:12]2[CH2:17][C@H:16]([C:18]3[O:22][NH:21][C:20](=[O:23])[CH:19]=3)[CH2:15][CH2:14][NH:13]2)[CH:5]=[CH:6][C:7]=1[C:8]([F:9])([F:10])[F:11]

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66732784HCID 66732784, compound

Product 1

HCID 46937525HCID 46937525, compoundYield 48%

Procedure

(2S,4R)-Methyl 2-(3-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (0.168 g, 0.44 mmol) (from example 67, step 3) was dissolved in HBr (33% in acetic acid, 5.6 g, 22.84 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-methyl-4-(trifluoromethyl)phenyl)piperidin-4-yl)isoxazol-3(2H)-one (0.068 g, 48%). 1H NMR (600 MHz, dmso) δ 1.31-1.40 (m, 1H), 1.41-1.50 (m, 1H), 1.85-1.90 (m, 1H), 1.95-2.00 (m, 1H), 2.40 (s, 3H), 2.69-2.76 (m, 1H), 2.83-2.90 (m, 1H), 3.08-3.13 (m, 1H), 3.68 (d, 1H), 5.73 (s, 1H), 7.36 (d, 1H), 7.43 (s, 1H), 7.57 (d, 1H). HRMS Calcd for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1318.

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-9feb5b9a533249c0bbf3cf55e990771e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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