Dimethylformamide → 6-Fluoro-1-methyl-1H-indazole-5-carbaldehyde

Temperature

-10 °C

A 2 M solution of n-butyl magnesium chloride in THF (4.8 mL, 9.57 mmol) was added to toluene (34 mL) under nitrogen and cooled to −10° C. To this was added a 1.3 M solution of n-butyl lithium in hexane (12.2 mL, 19.5 mmol) and after 1 h, the RM was cooled to −30° C. To the RM was then added a solution of 5-bromo-6-fluoro-1-methyl-1H-indazole (vii) (4 g, 17.73 mmol) in THF (17 mL) and the reaction was warmed up to −10° C. After 1 h, DMF (8.23 mL, 106 mmol) was added and the RM was stirred at −10° C. for another 1 h. The reaction was quenched using 2 N HCl and was allowed to warm up to room temperature. After 30 min, the RM was basified with saturated aqueous NaHCO3 solution and then extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and evaporated under vacuo. The residue was triturated with Et2O. The precipitate formed was filtered off to give a yellow solid identified as the desired aldehyde (tR 0.79 min (conditions 2), MH+=179).

1. temperaturethe RM was cooled to −30° C
2. temperaturethe reaction was warmed up to −10° C
3. waitAfter 1 h
4. customThe reaction was quenched
5. temperatureto warm up to room temperature
6. waitAfter 30 min
7. extractionextracted with EtOAc
8. washThe organic phase was washed with brine
9. dry with materialdried over Na2SO4
10. customevaporated under vacuo
11. customThe residue was triturated with Et2O
12. customThe precipitate formed
13. filtrationwas filtered off
14. customto give a yellow solid

ORD record

ord-a1eb844cfb2d4ca7b038add34ce7494d

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822468B2