Reaction #3113

Reaction equation

ethyl acetate

4-Cyanophenol

sodium chlorodifluoroacetate

sodium hydroxide

→

title compound

Yield 41.0%

4-difluoromethoxybenzonitrile

Yield 41.0%

Solvents

DMF

Conditions

Workup

1. 1
   Washthe organic layer was washed twice with brine
2. 2
   ExtractionThe organic extract
3. 3
   Dryingwas dried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Otherevaporated
6. 6
   OtherThe residue was purified by flash chromatography (silica gel, 25% ethyl acetate/hexanes)
7. 7
   Otherto provide a white solid
8. 8
   Other(1 mm Hg, 23° C.)

Procedure

4-Cyanophenol (0.50 g, 4.2 mmol, Aldrich), sodium chlorodifluoroacetate (0.77 g, 5 mmol, Alfa Products), and sodium hydroxide (0.20 g, 5 mmol) were combined in dry DMF (2 mL) under an atmosphere of argon. After stirring at 125°-130° C. for 5 h, the mixture was cooled to RT, ethyl acetate (50 mL) was added and the organic layer was washed twice with brine. The organic extract was dried (MgSO4), filtered and evaporated. The residue was purified by flash chromatography (silica gel, 25% ethyl acetate/hexanes) to provide a white solid. The solid was sublimed (1 mm Hg, 23° C.) to provide the title compound as colorless crystals (0.29 g, 41%). mp 33°-35° C.

Source