Reaction #2329012

Reaction equation

water

THF

4-fluoro-2-chloro-benzonitrile

potassium t-butoxide

THF

→

2-Chloro-4-(cis-2-hydroxy-cyclopentyloxy)-benzonitrile

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
   workup.ADDITIONpoured into a seperatory funnel
8. 8
   Extractionextracted with 20 mL of methyl tert-butyl ether
9. 9
   WashThe organic phase was washed with water, brine
10. 10
    Dryingdried (MgSO4)
11. 11
    Concentrationconcentrated in vacuo
12. 12
    Otherthe residue purified by reverse phase HPLC (Shimadzu)

Procedure

A 1.0 M solution of potassium t-butoxide in t-butanol (3.2 mL) was added to a 16 mL vial fitted with a septa cap containing 3 mL of dry THF and 300 mg (3 mmoles) of cis-1,2-dihydroxy cylcopentanol at 5° C. The mixture was stirred for 0.5 h at 5° C., after which time 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., poured into a seperatory funnel containing 15 mL of water, and extracted with 20 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 185 mg 2-Chloro-4-(cis-2-hydroxy-cyclopentyloxy)-benzonitrile. GC/MS: 237 (M/Z for C13H14ClNO).

Source