Acetic Acid → 2-(3,3-difluorocyclobutyl)-1H-benzo[d]imidazole

Participants

Reaction Steps

[step 2] 3,3-Difluoro-N-(2-nitrophenyl)cyclobutanecarboxamide (400 mg, 1.56 mmol) obtained in step 1 was dissolved in ethanol (10 mL), methanol (40 mL), and ethyl acetate (40 mL), and 10% Pd—C (120 mg) was added. The reaction system was purged with hydrogen gas, and the mixture was stirred at room temperature for 3 hr. After completion of the reaction, the reaction mixture was filtered through celite, and the solution was concentrated under reduced pressure. To the obtained residue was added acetic acid (2.2 mL, 38.4 mmol), and the mixture was stirred at 80° C. for 1 hr. Under ice-cooling, saturated aqueous sodium hydrogen carbonate was added to the mixture, and the mixture was extracted 3 times with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 v/v-30/70 v/v) to give 2-(3,3-difluorocyclobutyl)-1H-benzo[d]imidazole (135 mg, 42%).

Provenance & Evidence