Reaction #2329010

Reaction equation

potassium t-butoxide

THF

4-fluoro-2-chloro-benzonitrile

THF

3-hydroxy cylcopentanol

→

title compound

Yield 52.0%

2-Chloro-4-(3-methyl-cyclopentyloxy)-benzonitrile

Yield 52.0%

Solvents

t-butanol

Conditions

Workup

1. 1
   Othervial fitted with a septa
2. 2
   Othercap
3. 3
   workup.STIRRINGThe reaction was stirred at 5° C. for 3 h
4. 4
   Temperatureto warm to room temperature
5. 5
   workup.STIRRINGstirred overnight at room temperature
6. 6
   TemperatureThe reaction mixture was cooled to 0° C.
7. 7
   Otherquenched with 2 mL of water
8. 8
   workup.ADDITIONdiluted with 2 mL of methyl tert-butyl ether
9. 9
   workup.STIRRINGThe vial was shaken vigourously
10. 10
    Otherto separate
11. 11
    OtherThe aqueous layer was removed with a pipette
12. 12
    Washthe organic layer washed with another 2 mL of water
13. 13
    DryingThe organic phase was dried (MgSO4)
14. 14
    Concentrationconcentrated in vacuo
15. 15
    Otherthe residue purified by reverse phase HPLC (Shimadzu)

Procedure

A 1.0 M solution of potassium t-butoxide in t-butanol (0.3 mL) was added to a 8 mL vial fitted with a septa cap containing 0.3 mL of dry THF and 30 mg (0.3 mmoles) of 3-hydroxy cylcopentanol at 5° C. The mixture was stirred for 0.5 h at 5° C., after which time 0.3 mL of a 1.0 M THF solution of 4-fluoro-2-chloro-benzonitrile was added. The reaction was stirred at 5° C. for 3 h and then allowed to warm to room temperature and stirred overnight at room temperature. The reaction mixture was cooled to 0° C., and quenched with 2 mL of water, diluted with 2 mL of methyl tert-butyl ether. The vial was shaken vigourously and the phases allowed to separate. The aqueous layer was removed with a pipette, and the organic layer washed with another 2 mL of water. The organic phase was dried (MgSO4), concentrated in vacuo, and the residue purified by reverse phase HPLC (Shimadzu) to give 36 mg (52%) of the title compound. GC/MS: 235 (M/Z for C13H14ClNO).

Source