Tetrafluoroboric acid → 4-Fluoro-1H-indazole

Temperature

0 °C

To tetrafluoroboric acid (8.2 ml, 48 wt % in water) was added 3-fluoro-2-methylaniline (2.27 ml). The mixture was cooled to 0° C. when a precipitate formed which was redissolved by the addition of water (8 ml). A solution of sodium nitrite (1.38 g) in water (2.7 ml) was then added dropwise and the mixture was then allowed to warm to ambient temperature and then stirred for a further 1 hour. The precipitated solid was filtered, then washed with diethyl ether, and then dried under suction for 30 minutes. The resulting tetrafluoroborate salt was added to a suspension of potassium acetate (3.92 g) and 18-crown-6 (0.264 g) in chloroform (45 ml). After stirring for 3 hours at ambient temperature the bright orange mixture was filtered and the insoluble material was washed with dichloromethane, then subjected to flash column chromatography on silica eluting with a mixture of 40/60 petrol and ethyl acetate (3:1 v/v) to give 4-fluoro-1H-indazole (0.675 g) as an off-white solid. LC-MS (METHOD B): RT=2.70 minutes; 137 (M+H)+.

1. customformed which
2. temperatureto warm to ambient temperature
3. filtrationThe precipitated solid was filtered
4. washwashed with diethyl ether
5. customdried under suction for 30 minutes
6. additionThe resulting tetrafluoroborate salt was added to a suspension of potassium acetate (3.92 g) and 18-crown-6 (0.264 g) in chloroform (45 ml)
7. stirringAfter stirring for 3 hours at ambient temperature the bright orange mixture
8. filtrationwas filtered
9. washthe insoluble material was washed with dichloromethane
10. additionsubjected to flash column chromatography on silica eluting with a mixture of 40/60 petrol and ethyl acetate (3:1 v/v)

ORD record

ord-2ec9f10f679e47c4aca2a5570404df05

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288425B2