Reaction #6169

Reaction equation

1-(5-chloropentoxy)-2-methoxybenzene

potassium carbonate

4-Cyanophenol

potassium iodide

→

4-[5-(2-methoxyphenoxy)pentoxy]benzonitrile

Solvents

dimethyl sulfoxide

Conditions

Workup

1. 1
   workup.ADDITIONis added
2. 2
   TemperatureThis suspension is heated at 80°-82° C. for 7 hours
3. 3
   Otherthe heating bath is then removed
4. 4
   workup.ADDITIONthe mixture is poured onto cold water (29 L)
5. 5
   Otherthe product precipitates
6. 6
   ExtractionThis mixture is then extracted with ethyl acetate (3×20 L)
7. 7
   WashThe organic extracts are washed with potassium hydroxide solution (0.50N, 4×8 L), brine (2×10 L)
8. 8
   Dryingdried over anhydrous sodium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated in vacuo
11. 11
    Otherto yield a yellow oil which
12. 12
    Othercrystallizes
13. 13
    workup.DISSOLUTIONThis is then dissolved in 2-propanol (5.6 L)
14. 14
    Temperaturewith warming
15. 15
    Filtrationthe resulting solution is filtered gravimetrically
16. 16
    Washwashing the funnel with 1.2 L of hot 2-propanol
17. 17
    TemperatureThe combined filtrate is cooled to 10° C. in an ice bath
18. 18
    Filtrationfiltered
19. 19
    WashThe filter cake is washed with 2-propanol (2×800 mL)
20. 20
    Otherdried in vacuo

Procedure

4-Cyanophenol (742 g, 6.23 mol) is dissolved in dimethyl sulfoxide (7.30 L) and to this solution is added powdered anhydrous potassium carbonate (883 g, 6.30 mol), potassium iodide (1.05 kg, 6.30 mol) and finally 1-(5-chloropentoxy)-2-methoxybenzene (1.44 kg, 6.29 mol). This suspension is heated at 80°-82° C. for 7 hours and the heating bath is then removed. After stirring overnight at room temperature, the mixture is poured onto cold water (29 L) and the product precipitates. This mixture is then extracted with ethyl acetate (3×20 L). The organic extracts are washed with potassium hydroxide solution (0.50N, 4×8 L), brine (2×10 L), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to yield a yellow oil which crystallizes on standing. This is then dissolved in 2-propanol (5.6 L) with warming and the resulting solution is filtered gravimetrically, washing the funnel with 1.2 L of hot 2-propanol. The combined filtrate is cooled to 10° C. in an ice bath and the solid mass is broken up and filtered. The filter cake is washed with 2-propanol (2×800 mL), dried in vacuo to give 4-[5-(2-methoxyphenoxy)pentoxy]benzonitrile, m.p. 66°-68° C. which is >99.5% pure by glc analysis.

Source