Reaction #2329009

Reaction equation

Trans-2-Methylcylopentanol

2-Trifluoromethyl-4-fluoro-benzonitrile

water

→

4-(trans-2-Methyl-cyclopentyloxy)-2-trifluoromethyl-benzonitrile

Yield 83.2%

Solvents

THF

Conditions

Workup

1. 1
   Dryingdried round bottom flask under nitrogen containing 0.5 mL of dry tetrahydrofuran (“THF”)
2. 2
   workup.ADDITIONA 1.0 M solution of potassium t-butoxide in t-butanol (0.5 mL) was added dropwise
3. 3
   OtherThe above solution was then transferred via syringe to a flask
4. 4
   workup.STIRRINGThe mixture was stirred at 0° C. for 3 h
5. 5
   Temperaturewarmed to room temperature
6. 6
   workup.STIRRINGstirred for 16 h
7. 7
   TemperatureThe reaction mixture was then cooled to 0° C.
8. 8
   workup.ADDITIONpoured into a seperatory funnel
9. 9
   Extractionextracted with 10 mL of methyl tert-butyl ether
10. 10
    WashThe organic phase was washed with water, brine
11. 11
    Dryingdried (MgSO4)
12. 12
    Concentrationconcentrated in vacuo
13. 13
    Otherthe residue purified by reverse phase HPLC (Shimadzu)

Procedure

Trans-2-Methylcylopentanol (50 mg, 0.5 mmol) was added to a flame dried round bottom flask under nitrogen containing 0.5 mL of dry tetrahydrofuran (“THF”) and cooled to 0° C. A 1.0 M solution of potassium t-butoxide in t-butanol (0.5 mL) was added dropwise and the reaction mixture stirred at 0° C. for 0.5 h. The above solution was then transferred via syringe to a flask containing 2-Trifluoromethyl-4-fluoro-benzonitrile (95 mg, 0.5 mmol) in 0.5 mL of THF at 0° C. The mixture was stirred at 0° C. for 3 h, warmed to room temperature and stirred for 16 h. The reaction mixture was then cooled to 0° C., poured into a seperatory funnel containing 8 mL of water, and extracted with 10 mL of methyl tert-butyl ether. The organic phase was washed with water, brine, dried (MgSO4), concentrated in vacuo, and the residue purified by reverse phase HPLC (Shimadzu) to give 112 mg 4-(trans-2-Methyl-cyclopentyloxy)-2-trifluoromethyl-benzonitrile. GC/MS: 269 (M/Z for C14H14F3NO).

Source