Reacción #647380

Ecuación de reacción

sodiumborohydride

tert-Butyllithium

4-fluoroiodobenzene

1-Pyrrolidin-1-yl-cyclobutanecarbonitrile

1-pyrrolidin-1-yl-cyclobutanecarbonitrile

intermediate F

1-pyrrolidin-1-yl-cyclobutanecarbonitrile

sodium bicarbonate

→

title compound

Rendimiento 86.8%

C-(4-Fluorophenyl)-C-(1-pyrrolidin-1-yl-cyclobutyl)-methylamine

Rendimiento 86.8%

Disolventes

diethylether

diethylether

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato slowly warm up
2. 2
   ExtracciónThe mixture was extracted three times with ethyl acetate
3. 3
   OtroThe combined organic phases were dried on sodium sulfate
4. 4
   Filtraciónfiltered
5. 5
   Otroevaporated
6. 6
   workup.DISSOLUTIONThe residue was dissolved in 100 mL methanol
7. 7
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 2 hours
8. 8
   Otroquenched by addition of water
9. 9
   OtroThe solvent was evaporated off
10. 10
    Extracciónethyl acetate and was extracted three times with ethyl acetate
11. 11
    OtroThe combined organic phases were dried on sodium sulfate
12. 12
    Filtraciónfiltered
13. 13
    Otroevaporated
14. 14
    OtroPurification of the residue by flash chromatography on amine silica gel with dichloromethane

Procedimiento

tert-Butyllithium (1.6M in pentane, 65 mL, 104 mmol) was added during 30 min at −75° C. to −60° C. to a solution of 4-fluoroiodobenzene (13 g, 59 mmol) in 40 mL diethylether. The reaction mixture was stirred at −75° C. for 45 min. 1-Pyrrolidin-1-yl-cyclobutanecarbonitrile (intermediate F) (5 g, 29 mmol) in 5 mL diethylether was added slowly. The reaction mixture was allowed to slowly warm up and was poured into cold saturated sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. The residue was dissolved in 100 mL methanol and sodiumborohydride (2.3 g, 59 mmol) was added portion-wise at 0° C. The reaction mixture was stirred at room temperature for 2 hours and quenched by addition of water. The solvent was evaporated off. The residue was taken up in water and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on amine silica gel with dichloromethane yielded the title compound as a yellow oil (6.25 g, 85%), MS: m/e=249.2 [(M+H)+].

Fuente