Hydrochloric Acid → 4-fluoro-1H-indazole-5-carbaldehyde

To a mixture of 5-bromo-4-fluoro-1H-indazole (4 mmol) and sodium hydride (4.3 mmol) in an Argon-purged round-bottom flask was added dry THF (10 mL) at rt. The mixture was stirred at rt for 15 min, during which time it became homogeneous (dark brown). The mixture was then cooled to −78° C., and a solution of n-butyllithium (8.7 mmol, 1.6 M in hexane) was added dropwise. After stirring for 1 h at −78° C., DMF (2 mL) was added dropwise and the mixture was allowed to warm to rt. After 3 h, the mixture was cooled to 0° C. and carefully treated with 1N HCl (20 mL). After a few minutes, solid sodium bicarbonate was added to basify the mixture to pH9-10. The aqueous solution was extracted with EtOAc(2×), and the organic layer was washed with brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (0-40% EtOAc/hexanes) to give 4-fluoro-1H-indazole-5-carbaldehyde.

1. custompurged round-bottom flask
2. additionwas added dry THF (10 mL) at rt
3. temperatureThe mixture was then cooled to −78° C.
4. stirringAfter stirring for 1 h at −78° C.
5. temperatureto warm to rt
6. waitAfter 3 h
7. temperaturethe mixture was cooled to 0° C.
8. waitAfter a few minutes
9. extractionThe aqueous solution was extracted with EtOAc(2×)
10. washthe organic layer was washed with brine
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated
13. customThe residue was purified by flash chromatography (0-40% EtOAc/hexanes)

ORD record

ord-33d646213a584b61b9e0e10cbb52363c

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796256B2