Hydrazine → 6-Chloro-4-fluoro-1H-indazole

Temperature

35 °C

4-Chloro-2,6-difluoro-benzaldehyde (15 g, 85 mmol) was dissolved in 1,2-dimethoxyethane 170 ml). O-Methyl-hydroxylamine hydrochloride (7.1 g, 85 mmol) and potassium carbonate (12.9 g, 93.5 mmol) were then added and the mixture was stirred at 35° C. for 24 h. The reaction was filtered, rinsed with dichloromethane, evaporated and redissolved in DMF (170 ml). Hydrazine (2.9 ml 93.5 mmol) was added and the reaction was stirred at 100° C. for 1 h. After cooling, water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with water and sodium chloride solution then dried over sodium sulfate. The solvent was evaporated to leave a solid which was purified by silica gel chromatography (diethyl ether/hexanes) to give 7 g (49%) of 6-chloro-4-fluoro-1H-indazole. (M+H)+=171.

1. filtrationThe reaction was filtered
2. washrinsed with dichloromethane
3. customevaporated
4. dissolutionredissolved in DMF (170 ml)
5. stirringthe reaction was stirred at 100° C. for 1 h
6. temperatureAfter cooling
7. customThe layers were separated
8. extractionthe aqueous layer was extracted twice more with ethyl acetate
9. washThe combined organic layers were washed with water and sodium chloride solution
10. dry with materialthen dried over sodium sulfate
11. customThe solvent was evaporated
12. customto leave a solid which
13. customwas purified by silica gel chromatography (diethyl ether/hexanes)

ORD record

ord-f933b270f33146b0a18369b5faf035e5

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2