Dimethylformamide → 5-Fluoro-1H-indazole-7-carboxaldehyde

Temperature

-78 °C

To a solution of 7-bromo-5-fluoro-1H-indazole (1.66 g, 7.72 mmol) in tetrahydrofuran (35 mL) at 0° C. was added sodium hydride (0.618 g, 15.4 mmol). The ice bath was removed and stirring continued for 20 min. The solution was cooled to -78° C. and treated with tert-butyllithium (1.7 M in pentane, 9.08 mL, 15.4 mmol) dropwise. The reaction was stirred at −78° C. for 10 min, allowed to warm gradually in the dewar to −50° C., recooled to −78° C., and then treated with dimethylformamide (2.39 mL, 30.9 mmol). After 15 min, the ice bath was removed and stirring continued for 1 h. The reaction was poured onto ice/I M hydrochloric acid (26.5 mL). The mixture was extracted with ethyl acetate (2×). The organics were washed with water, then brine, dried over magnesium sulfate, and concentrated to give 1.42 g of 5-fluoro-1H-indazole-7-carbaldehyde (quant.) as a light yellow solid. LC/MS (HPLC method 3): tR=1.39 min, 165.17(MH)+.

1. customThe ice bath was removed
2. stirringThe reaction was stirred at −78° C. for 10 min
3. temperatureto warm gradually in the dewar to −50° C.
4. customrecooled to −78° C.
5. waitAfter 15 min
6. customthe ice bath was removed
7. stirringstirring
8. waitcontinued for 1 h
9. additionThe reaction was poured onto ice/I M hydrochloric acid (26.5 mL)
10. extractionThe mixture was extracted with ethyl acetate (2×)
11. washThe organics were washed with water
12. dry with materialbrine, dried over magnesium sulfate
13. concentrationconcentrated

ORD record

ord-d595bad8ef014d7cad5db7aec10338ab

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026257B2