Reacción #1342813

Ecuación de reacción

4-[4-bromo-3-(2-tetrahydropyranyloxymethyl)phenoxy]-3-(hydroxymethyl)benzonitrile

triethylamine

methanesulfonyl chloride

ethyl acetate water

→

4-[4-bromo-3-(2-tetrahydropyranyloxymethyl)phenoxy]-3-(formylaminomethyl)benzonitrile

Rendimiento 68.1%

Disolventes

N,N-dimethylformamide

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   LavadoThe mixture was washed with water and brine
2. 2
   Secadodried on anhydrous sodium sulfate
3. 3
   OtroThe solvent was removed under reduced pressure
4. 4
   workup.STIRRINGthe mixture was stirred at 50° C. for 2 h
5. 5
   LavadoThe organic layer was washed with brine
6. 6
   Secadodried on anhydrous sodium sulfate
7. 7
   OtroThe solvent was removed under reduced pressure
8. 8
   workup.ADDITIONTo a solution of the residue in 1,4-dioxane (80 mL) was added 3 M NaOH (10 mL)
9. 9
   workup.STIRRINGthe mixture was stirred at room temperature for 1 h
10. 10
    workup.ADDITIONThe mixture was poured into ethyl acetate/water
11. 11
    LavadoThe organic layer was washed with brine
12. 12
    Secadodried on anhydrous sodium sulfate
13. 13
    OtroThe solvent was removed under reduced pressure
14. 14
    OtroThe residue was purified by silica gel column (5:5 to 4:6 hexane/ethyl acetate)

Procedimiento

To a solution of 4-[4-bromo-3-(2-tetrahydropyranyloxymethyl)phenoxy]-3-(hydroxymethyl)benzonitrile (12.1 g, 28.9 mmol) in dichloromethane (100 mL) were added triethylamine (8.0 mL, 58 mmol) and methanesulfonyl chloride (2.5 mL, 32 mmol) at 0° C., and the mixture was stirred at room temperature for 1 h. The mixture was washed with water and brine, and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. To a solution of the residue in N,N-dimethylformamide (100 mL) was added sodium diformylimide (3.29 g, 34.7 mmol), and the mixture was stirred at 50° C. for 2 h. The mixture was poured into ethyl acetate/water. The organic layer was washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. To a solution of the residue in 1,4-dioxane (80 mL) was added 3 M NaOH (10 mL), and the mixture was stirred at room temperature for 1 h. The mixture was poured into ethyl acetate/water. The organic layer was washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column (5:5 to 4:6 hexane/ethyl acetate) to give 4-[4-bromo-3-(2-tetrahydropyranyloxymethyl)phenoxy]-3-(formylaminomethyl)benzonitrile (8.77 g, 68%).

Fuente