Acetic Anhydride → 4-bromo-1H-indazole

To a solution of 3-bromo-2-methylaniline (5 g, 27 mmol) in chloroform (1 mL) was added acetic anhydride (5 g, 27 mmol) at 0° C. and the mixture was stirred at room temperature for 1 h. Potassium acetate (0.75 g, 7.8 mmol) and isoamyl nitrite (0.78 g, 58 mmol) were added and the reaction mixture was refluxed for 18 h. The volatiles were removed under reduced pressure and water (0.65 mL) was added. The mixture was concentrated, diluted with concentrated hydrochloride acid (1 mL) and heated at 50° C. for 2 h. After being cooled to room temperature, aqueous sodium hydroxide solution (50%) was added until pH=10. The aqueous mixture was extracted with ethyl acetate (100 mL×3). The combined organic layer was washed with brine (150 mL), dried over anhydrous sodium sulfate, filtered, evaporated and purified on silica gel column (3% ethyl acetate in petroleum ether) to give the desired product (2.69 g, 34% yield) as a solid. MS (ESI): m/z 197.0 [M+1]+.

1. temperaturethe reaction mixture was refluxed for 18 h
2. customThe volatiles were removed under reduced pressure and water (0.65 mL)
3. additionwas added
4. concentrationThe mixture was concentrated
5. additiondiluted with concentrated hydrochloride acid (1 mL)
6. temperatureheated at 50° C. for 2 h
7. temperatureAfter being cooled to room temperature
8. additionaqueous sodium hydroxide solution (50%) was added until pH=10
9. extractionThe aqueous mixture was extracted with ethyl acetate (100 mL×3)
10. washThe combined organic layer was washed with brine (150 mL)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationfiltered
13. customevaporated
14. custompurified on silica gel column (3% ethyl acetate in petroleum ether)

ORD record

ord-036c99ed74c74cb0b08b15db8fc1b7cf

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507492B2