Reaction #69061

Reaction equation

3-Cyanophenol

potassium carbonate

potassium iodide

(chloromethyl)cyclopropane

→

title compound

(3-(cyclopropylmethoxy)phenyl)methanamine

Solvents

DMF

water

N,N-dimethylformamide

Conditions

Workup

1. 1
   Extractionthe resultant mixture was then extracted with toluene (130 mL)
2. 2
   WashThe organic layer was washed with brine (100 mL)
3. 3
   Dryingdried over anhydrous sodium sulfate
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (hereinafter,
6. 6
   workup.ADDITIONwas gradually added dropwise at 0° C.
7. 7
   workup.STIRRINGthe reaction mixture was then stirred at 45° C. for 4 hours
8. 8
   workup.ADDITIONTo the reaction mixture, water (10 mL), an aqueous sodium hydroxide solution (1.0 M, 10 mL), and water (5.0 mL) were gradually added at 0° C
9. 9
   OtherThe resultant precipitate was removed by filtration
10. 10
    Washwashed with 10% methanol/THF (400 mL)
11. 11
    ConcentrationThen, the combined filtrate was concentrated under reduced pressure
12. 12
    workup.ADDITIONTo the residue, water (50 mL) was added
13. 13
    Extractionthe resultant mixture was then extracted with ethyl acetate (50 mL×3)
14. 14
    WashThe organic layer was washed with brine (50 mL)
15. 15
    Dryingdried over anhydrous sodium sulfate
16. 16
    Concentrationconcentrated under reduced pressure

Procedure

3-Cyanophenol (12.4 g) was dissolved in N,N-dimethylformamide (hereinafter, referred to as DMF; 100 mL). To the solution, potassium carbonate (30.5 g), potassium iodide (1.74 g), and (chloromethyl)cyclopropane (10.2 mL) were added, and the mixture was stirred at 90° C. for 4 hours. To the reaction mixture, water (130 mL) was added, and the resultant mixture was then extracted with toluene (130 mL). The organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (hereinafter, referred to as THF; 60 mL). To the solution, a solution of lithium aluminum hydride (hereinafter, referred to as LAH) in THF (2.4 M, 68 mL) was gradually added dropwise at 0° C., and the reaction mixture was then stirred at 45° C. for 4 hours. To the reaction mixture, water (10 mL), an aqueous sodium hydroxide solution (1.0 M, 10 mL), and water (5.0 mL) were gradually added at 0° C. The resultant precipitate was removed by filtration and washed with 10% methanol/THF (400 mL). Then, the combined filtrate was concentrated under reduced pressure. To the residue, water (50 mL) was added, and the resultant mixture was then extracted with ethyl acetate (50 mL×3). The organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain the title compound (18.1 g) as a crude product.

Source