Hydrochloric Acid → 5-Bromo-7-fluoro-2-methyl-1H-benzimidazole

A round bottomed flask was charged with 5-bromo-3-fluorobenzene-1.2 diamine (400 mg, 2 mmol) and 30 mL ethanol. 5 N hydrochloric acid (8 mL, 40 mmol) was then added. This mixture was heated to reflux and 2,4-pentanedione was added. The reaction mixture turned deep purple in color then slowly turned back to tan. Reaction was allowed to proceed for 3 hours and then cooled and neutralized with saturated sodium bicarbonate solution. The reaction mixture was then extracted three times with dichloromethane. The combined organic layers were washed with brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The crude mixture was triturated in diethyl ether then filtered to give 6-bromo-4-fluoro-2-methyl-1H-benzo[d]imidazole (375 mg, 82%) as a tan solid, 1H NMR (400 MHz, CDCl3) δ ppm 7.44 (br. s., 1H), 7.10 (d, J=11.22 Hz, 1H), 2.63 (s, 3H).

1. temperatureThis mixture was heated
2. temperatureto reflux
3. customReaction
4. temperaturecooled
5. extractionThe reaction mixture was then extracted three times with dichloromethane
6. washThe combined organic layers were washed with brine
7. dry with materialdried with magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude mixture was triturated in diethyl ether
11. filtrationthen filtered

ORD record

ord-e69efe612b274e64b717b47929b5d74d

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507681B2