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

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 stirred at ambient temperature for 30 minutes, cooled to 0° C. and treated dropwise with 2-trimethylsilylethyoxymethyl chloride (13.7 mL, 12.86 g, 77 mmol). The mixture was stirred at ambient temperature for 18 hours and quenched by the addition of saturated ammonium chloride solution. The mixture was diluted with water and concentrated in vacuo to remove tetrahydrofuran. The residue was diluted with ethyl acetate and the organic layer was washed with saturated sodium chloride solution, dried (Na2SO4), filtered and concentrated in vacuo to afford an orange oil. Distillation (93-94° C./0.2 mm Hg) afforded the title compound as a colorless liquid (12.97 g, 89%). MS (ESI+) m/z 199 (M+H)+.

1. temperaturecooled to 0° C.
2. stirringThe mixture was stirred at ambient temperature for 18 hours
3. customquenched by the addition of saturated ammonium chloride solution
4. additionThe mixture was diluted with water
5. concentrationconcentrated in vacuo
6. customto remove tetrahydrofuran
7. additionThe residue was diluted with ethyl acetate
8. washthe organic layer was washed with saturated sodium chloride solution
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto afford an orange oil
13. distillationDistillation (93-94° C./0.2 mm Hg)

ORD record

ord-d8cf098e5fcf42a49625236d69d6abbe

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09173887B2