2-Amino-4-fluorophenol → 2-(3,5-Dimethyl-1H-pyrazol-1-yl)-4-fluorophenol

To 100 mg of 2-amino-4-fluorophenol was added 0.8 ml of 5N-hydrochloric acid, and a solution in which 65 mg of sodium nitrite was dissolved in 0.2 ml of water was added dropwise at 0° C., and stirred for 30 minutes. Then, a solution in which 249 mg of stannous chloride was dissolved in 0.46 ml of 5N-hydrochloric acid, was added dropwise at 0° C., and stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 2.5 ml of ethanol and 81 μl of acetyl acetone were added, followed by heating at reflux for 4 hours. To the reaction mixture was added 50 ml of water, neutralized with a saturated solution of sodium hydrogen carbonate, and extracted with 50 ml of ethyl acetate. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure and purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1) to yield 20.6 mg of the title compound.

1. additionwas added dropwise at 0° C.
2. additionwas added dropwise at 0° C.
3. stirringstirred at 0° C. for 30 minutes
4. waitat room temperature for 2 hours
5. distillationThe solvent was distilled off under reduced pressure, and 2.5 ml of ethanol and 81 μl of acetyl acetone
6. additionwere added
7. temperatureby heating
8. temperatureat reflux for 4 hours
9. additionTo the reaction mixture was added 50 ml of water
10. extractionextracted with 50 ml of ethyl acetate
11. dry with materialAfter the organic layer was dried over anhydrous magnesium sulfate
12. distillationthe solvent was distilled off under reduced pressure
13. custompurified by silica gel column chromatography (n-hexane:ethyl acetate=2:1)

ORD record

ord-f19818f5795c48648c5e261910e7beae

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889727B2