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

[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%).

1. customThe reaction system was purged with hydrogen gas
2. customAfter completion of the reaction
3. filtrationthe reaction mixture was filtered through celite
4. concentrationthe solution was concentrated under reduced pressure
5. stirringthe mixture was stirred at 80° C. for 1 hr
6. temperatureUnder ice-cooling
7. extractionthe mixture was extracted 3 times with ethyl acetate
8. washThe combined organic layers were washed with water
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 v/v-30/70 v/v)

ORD record

ord-14069a8847d44791ad7463b72c074ea8

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969345B2