Reaction #74624

Reaction equation

1-(benzyloxy)-2-bromo-4-(trifluoromethoxy)benzene

(1-methyl-1H-pyrazol-5-yl)boronic acid

tricyclohexylphosphine

tripotassium phosphate

→

title compound

Yield 70.0%

5-[2-(Benzyloxy)-5-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrazole

Yield 70.0%

Solvents

dioxane

water

Conditions

Workup

1. 1
   OtherReaction mixture
2. 2
   Temperaturewas refluxed for 16 hours
3. 3
   Filtrationfiltering through Celite™
4. 4
   ConcentrationThe filtrate was concentrated in vacuo
5. 5
   workup.ADDITIONthe residue was diluted with ethyl acetate (100 mL)
6. 6
   ExtractionThe organic extract
7. 7
   Washwas washed with water, saturated aqueous sodium chloride solution
8. 8
   Dryingdried over sodium sulfate
9. 9
   Concentrationconcentrated in vacuo
10. 10
    OtherPurification by silica gel column chromatography
11. 11
    Washeluting with ethyl acetate:hexane (1:9, by volume)

Procedure

A solution of 1-(benzyloxy)-2-bromo-4-(trifluoromethoxy)benzene (Preparation 535, 3.3 g, 9.5 mmol) and (1-methyl-1H-pyrazol-5-yl)boronic acid (Preparation 403, 1.2 g, 9.5 mmol) 1,4-in dioxane (25 mL) was degassed under argon for 30 minutes. Under argon, (1E,4E)-1,5-Diphenylpenta-1,4-dien-3-one-palladium (3:2) (348 mg, 0.38 mmol) and tricyclohexylphosphine (213 mg, 0.76 mmol) were added followed by the dropwise addition of a degassed solution of tripotassium phosphate (4 g, 19 mmol) in water (12.6 mL). Reaction mixture was refluxed for 16 hours before cooling to room temperature and filtering through Celite™. The filtrate was concentrated in vacuo and the residue was diluted with ethyl acetate (100 mL). The organic extract was washed with water, saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. Purification by silica gel column chromatography eluting with ethyl acetate:hexane (1:9, by volume) afforded the title compound, 2.3 g, 70% yield.

Source