Water → 5-bromo-3-chloro-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridine

HRID 623917Notes

Reaction equation

HRID 623917 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([Cl:17])[C:5]([C:8]2[NH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][N:12]=2)=[N:6][CH:7]=1.[H-].[Na+].[CH3:20][Si:21]([CH3:28])([CH3:27])[CH2:22][CH2:23][O:24][CH2:25]Cl.O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]([Cl:17])[C:5]([C:8]2[N:12]([CH2:25][O:24][CH2:23][CH2:22][Si:21]([CH3:28])([CH3:27])[CH3:20])[CH:11]=[C:10]([C:13]([F:14])([F:15])[F:16])[N:9]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 679752705-bromo-3-chloro-2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridine

Product 1

HCID 679736045-bromo-3-chloro-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In N,N-dimethylformamide (13 mL) was dissolved 5-bromo-3-chloro-2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridine (1.27 g), 60% sodium hydride (187 mg) was added to the solution under ice-cooling, and after raising the mixture to room temperature, the mixture was stirred for 1 hour. The reaction mixture was ice-cooled, 2-(trimethylsilyl)ethoxymethyl chloride (1.03 mL) was added to the mixture, and after raising the mixture to room temperature, the mixture was stirred for 1 hour. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with water and a saturated brine, and dried over anhydrous magnesium sulfate. After concentrating the mixture under reduced pressure, the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 95:5) to obtain 5-bromo-3-chloro-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridine (1.56 g).

Workup

  1. additionwas added to the solution under ice-
  2. temperaturecooling
  3. temperaturecooled
  4. temperatureafter raising the mixture to room temperature
  5. stirringthe mixture was stirred for 1 hour
  6. extractionthe mixture was extracted with ethyl acetate
  7. washthe organic layer was washed with water
  8. dry with materiala saturated brine, and dried over anhydrous magnesium sulfate
  9. concentrationAfter concentrating the mixture under reduced pressure
  10. customthe obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 95:5)

Sources & evidence

ORD record
ord-3b56a2fc6b514f388acec5fd23dbbd49
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

Loading…