2-Chloromethyl 2-(trimethylsilyl)ethyl ether → 5-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole

Temperature

25 °C

To a solution of 4-methylimidazole (2.70 g, 33.0 mmol) in 10 mL of acetonitrile at 0° C. was added NEt3 (4.00 g, 39.6 mmol) and acetyl chloride (2.80 g, 36.3 mmol). The mixture was allowed to attain RT then filtered to remove the ppt and the filtrate was concentrated to give 1-(4-methyl-imidazol-1-yl)-ethanone, which was used without further purification in the next step. To a solution of 1-(4-methyl-imidazol-1-yl)-ethanone (4.10 g, 33.0 mmol) in 15 mL acetonitrile was added SEM-Cl (5.80 g, 35.0 mmol) and the solution was stirred at 25° C. for 10 h. The solvents were removed by evaporation and to the residue was added 100 mL of 2.5 M NaOH and the mixture was stirred at 25° C. for 1 h. The reaction mixture was then extracted with ether (3×100 mL), dried over Na2SO4 and concentrated. The title compound was purified by chromatography on Silica gel eluting with 75% EtOAc/hexanes to give 4.30 g (61%) of a colorless oil: Mass spectrum (ESI, m/z): Calcd. for C10H20N2O4Si, 213.1 (M+H). found 213.1.

1. customwas used without further purification in the next step
2. customThe solvents were removed by evaporation and to the residue
3. additionwas added 100 mL of 2.5 M NaOH
4. stirringthe mixture was stirred at 25° C. for 1 h
5. extractionThe reaction mixture was then extracted with ether (3×100 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customThe title compound was purified by chromatography on Silica gel eluting with 75% EtOAc/hexanes

ORD record

ord-1ae91e1f8dd24e47bb9b17755799ec2f

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08674100B2