Sodium hydride → 2-Bromo-4,5-dichloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole

HRID 1874889Notes

Reaction equation

HRID 1874889 reaction equation
[Br:1][C:2]1[NH:3][C:4]([Cl:8])=[C:5]([Cl:7])[N:6]=1.[H-].[Na+].Cl[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17].C([O-])(O)=O.[Na+]>C1COCC1>[Br:1][C:2]1[N:3]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:4]([Cl:8])=[C:5]([Cl:7])[N:6]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 994842-Bromo-4,5-dichloro-1H-imidazoleHCID 516892Sodium BicarbonateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 586258532-Bromo-4,5-dichloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazoleYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-bromo-4,5-dichloro-1H-imidazole (2.16 g, 10 mmol) in THF (25 mL) was added dropwise to a suspension of NaH (440 mg of a 60% suspension in mineral oil, 11 mmol) in THF (20 mL) at 0° C. The mixture was stirred at RT for 2 h, cooled to 0° C. and {2-[(chloromethyl)oxy]ethyl}(trimethyl)silane (1.9 mL, 11 mmol) was added dropwise. The mixture was stirred at RT overnight. Saturated NaHCO3 was added and the aqueous layer was extracted with CH2Cl2. The organic layer was dried (Na2SO4), filtered, concentrated and purified by silica gel chromatography (0-50% CH2Cl2/hexanes) to give the title compound (3.26 g, 95%) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 5.26 (2H, s) 3.55-3.61 (2H, m) 0.88-0.94 (2H, m) −0.02 (9H, s). LCMS: m/z 346 (M+1).

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe mixture was stirred at RT overnight
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (0-50% CH2Cl2/hexanes)

Sources & evidence

ORD record
ord-d5ac7010441044a084068eb38183891d
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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