2-Bromopropane → 4-Bromo-1-(1-methylethyl)-1H-imidazole

Temperature

0 °C

A mixture of 4-bromo-1H-imidazole (1.0 g, 6.80 mmol) in dimethylformamide (5 mL) was stirred at 0° C., to which was added sodium hydride, 60% suspension in oil, (326 mg, 8.20 mmol). The reaction mixture was warmed to room temperature and stirred for 30 minutes, followed by dropwise addition of 2-bromopropane (0.70 mL, 7.48 mmol). The reaction mixture was stirred at room temperature for 15 hours under nitrogen, then quenched with water (10 mL) and extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with water (20 mL) and extracted with 1M hydrochloric acid (3×20 mL). The combined acidic extracts were washed with ethyl acetate (20 mL), then basified with ammonium hydroxide (pH 12), and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Preparative HPLC, eluting with an ethyl acetate-isohexane gradient, gave the product as a pale brown oil (380 mg, 30%).

1. temperatureThe reaction mixture was warmed to room temperature
2. stirringstirred for 30 minutes
3. stirringThe reaction mixture was stirred at room temperature for 15 hours under nitrogen
4. customquenched with water (10 mL)
5. extractionextracted with ethyl acetate (3×15 mL)
6. washThe combined organic extracts were washed with water (20 mL)
7. extractionextracted with 1M hydrochloric acid (3×20 mL)
8. washThe combined acidic extracts were washed with ethyl acetate (20 mL)
9. extractionextracted with ethyl acetate (3×20 mL)
10. dry with materialThe combined organic extracts were dried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. washPreparative HPLC, eluting with an ethyl acetate-isohexane gradient

ORD record

ord-5dd1bccd855d4b84a4568092ba950c96

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07041689B2