Reaction #2329016

Reaction equation

Cyclohexene oxide

4-fluoro-2-(trifluoromethyl)benzonitrile

potassium carbonate

water

→

4-(2-hydroxy-cyclohexyloxy)-2-trifluoromethyl-benzonitrile

Yield 50.0%

Solvents

DMF

Conditions

Workup

1. 1
   Temperatureto cool
2. 2
   Extractionextracted with ethyl acetate (200 mL) three times
3. 3
   WashThe combined extracts were washed with water (300 mL), 0.5M NaOH (300 mL), water (300 mL)
4. 4
   DryingThe organic phase was dried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Otherevaporated
7. 7
   OtherThe crude material was purified by chromatography on silica
8. 8
   Washeluting with a 2:1 solution of hexane

Procedure

Cyclohexene oxide (13.11 g, 133.6 mmol), 4-fluoro-2-(trifluoromethyl)benzonitrile (5.00 g, 26.72 mmol), and potassium carbonate (5.539 g, 40.08 mmol) in DMF (dimethylformamide) (50 mL) were heated to 95° C. for 14 hours. The reaction was then allowed to cool. The reaction was added to water (300 mL) and then extracted with ethyl acetate (200 mL) three times. The combined extracts were washed with water (300 mL), 0.5M NaOH (300 mL), water (300 mL), and a 15% sodium chloride solution (300 mL). The organic phase was dried over sodium sulfate, filtered and evaporated. The crude material was purified by chromatography on silica, eluting with a 2:1 solution of hexane:ethyl acetate. This yielded the desired product, 4-(2-hydroxy-cyclohexyloxy)-2-trifluoromethyl-benzonitrile (3.8 g, 50% yield).

Source