Methyl iodide → 4-(tert-butyl-dimethyl-silanyloxymethyl)-1-(4-fluoro-phenyl)-2-methyl-1H-imidazole

Temperature

-25 °C

4-(tert-Butyl-dimethyl-silanyloxymethyl)-1-(4-fluoro-phenyl)-1H-imidazole (18.2 g, 59.2 mmol) was dissolved in 600 mL dry THF and cooled to −78° C. n-Butyl lithium (55.5 mL, 1.6M in hexane, 88.8 mmol) was added dropwise. The reaction mixture was warmed up to −25° C., kept at −25° C. for 10 min and then cooled again to −78° C. Iodomethane (7.4 mL, 11.8 mmol) was added dropwise. The reaction mixture was slowly warmed up to room temperature and stirred at room temperature overnight. The solvent was evaporated. The residue was taken up in 300 mL water and extracted three times with ethyl acetate (200 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by column chromatography on silica gel (cyclohexane/ethyl acetate 50:50->20:80 gradient) and the desired compound was obtained as an orange oil (14.7 g, 77%), MS: m/e=321.1 (M+H+).

1. additionwas added dropwise
2. temperaturecooled again to −78° C
3. temperatureThe reaction mixture was slowly warmed up to room temperature
4. customThe solvent was evaporated
5. extractionextracted three times with ethyl acetate (200 mL each)
6. dry with materialThe combined organic extracts were dried with magnesium sulfate
7. filtrationfiltered
8. customevaporated
9. customThe crude product was purified by column chromatography on silica gel (cyclohexane/ethyl acetate 50:50->20:80 gradient)

ORD record

ord-63b4e4dab8de4d6d862df97022e2cab5

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07531529B2