Imidazole → 1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-imidazole

HRID 705395Notes

Reaction equation

HRID 705395 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[CH3:8][Si:9]([CH3:16])([CH3:15])[CH2:10][CH2:11][O:12][CH2:13]Cl>O1CCCC1>[CH3:8][Si:9]([CH3:16])([CH3:15])[CH2:10][CH2:11][O:12][CH2:13][N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 110526051-((2-(Trimethylsilyl)ethoxy)methyl)-1H-imidazoleYield 89.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of sodium hydride (3.08 g of 60% in oil, 1.85 g, 77 mmol) in dry tetrahydrofuran (80 mL) at 0° C. was treated dropwise with a solution of imidazole (5.00 g, 73.4 mmol) in dry tetrahydrofuran (20 mL) over 15 minutes. The mixture was warmed at room temperature for 30 minutes, followed by cooling again to 0° C. and addition of 2-trimethylsilylethyoxymethyl chloride (13.7 mL, 12.86 g, 77 mmol) dropwise. The mixture was allowed to warm to room temperature for 18 hours, and was quenched by addition of saturated ammonium chloride solution. The mixture was diluted with water and concentrated in vacuo to remove tetrahydrofuran. The residue was extracted with ethyl acetate and the organic layer was extracted with saturated sodium chloride solution. Drying (Na2SO4), filtration, and concentration in vacuo afforded an orange oil, which was distilled (93-94° C./0.2 mm Hg) to afford the title compound (12.97 g, 89%) as a colorless liquid. MS (ESI+) m/z (rel abundance) 199 (100, M+H)+.

Workup

  1. temperatureby cooling again to 0° C.
  2. temperatureto warm to room temperature for 18 hours
  3. customwas quenched by addition of saturated ammonium chloride solution
  4. additionThe mixture was diluted with water
  5. concentrationconcentrated in vacuo
  6. customto remove tetrahydrofuran
  7. extractionThe residue was extracted with ethyl acetate
  8. extractionthe organic layer was extracted with saturated sodium chloride solution
  9. customDrying
  10. filtration(Na2SO4), filtration, and concentration in vacuo
  11. customafforded an orange oil, which
  12. distillationwas distilled (93-94° C./0.2 mm Hg)

Sources & evidence

ORD record
ord-fa01f52c6c3441e4a0ce7b1a77225402
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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