反应详情

温度

-40 °C

805 mg (5 mmols) 4-fluoro-1H-indazole-5-carbonitrile (see EP 1510516, Example 85) were suspended in 25 mL toluene and cooled to −40° C. During 15 minutes 8 mL of a 1.5 M solution of diisobutylaluminium hydride in toluene (12 mmols) were added dropwise. The mixture was stirred for 2 hours at −40° C. At this temperature 5 mL ethyl acetate were added and the mixture was stirred for 20 minutes. 5 mL of a 1 M aqueous solution of tartaric acid were added and the mixture was stirred for 30 minutes at −20 to 0° C. The insolubles were removed by filtration. A small amount of dilute aqueous citric acid was added and the mixture was extracted with ethyl acetate. The extracts were washed with saturated sodium chloride and sodium hydrogen carbonate solutions and dried over sodium sulfate. The crude product was purified with column chromatography to yield 4-fluoro-1H-indazole-5-carbaldehyde 762 mg (92.9%). 1H-NMR (DMSO-d6): 13.82 (br s, 1H); 10.32 (s, 1H); 8.44 (s, 1H); 7.74 (dd, 1H); 7.49 (d, 1H) ppm.

1. stirringthe mixture was stirred for 20 minutes
2. stirringthe mixture was stirred for 30 minutes at −20 to 0° C
3. customThe insolubles were removed by filtration
4. additionA small amount of dilute aqueous citric acid was added
5. extractionthe mixture was extracted with ethyl acetate
6. washThe extracts were washed with saturated sodium chloride and sodium hydrogen carbonate solutions
7. dry with materialdried over sodium sulfate
8. customThe crude product was purified with column chromatography