Sodium hydride → 4-trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole

Temperature

0 °C

Into a 250-mL three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-(trifluoromethyl)-1H-imidazole (compound 216.1, 5 g, 36.74 mmol) in tetrahydrofuran (100 mL). This was followed by the addition of sodium hydride (1.6 g, 40.00 mmol, 60%) in portions at 0° C. and stirred for 1 h at 0° C. To this was added SEMCl (7.1 mL, 40.36 mmol) dropwise at 0° C. The resulting solution was stirred for 4 h at 0° C., then carefully quenched with 100 mL of brine. The pH of the solution was adjusted to 7-8 with hydrogen chloride (1 M). The aqueous phase was extracted with 2×100 mL of ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:5) as eluent to furnish 6 g (61%) of the title compound as a light yellow oil.

1. customInto a 250-mL three neck round-bottom flask, which was purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. stirringThe resulting solution was stirred for 4 h at 0° C.
4. customcarefully quenched with 100 mL of brine
5. extractionThe aqueous phase was extracted with 2×100 mL of ethyl acetate
6. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:5) as eluent

ORD record

ord-1dd4018463e6494f9660d276ab432135

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2