Reacción #8208

Ecuación de reacción

2-bromo-4,6-difluoro-N-carbethoxy aniline

triethyl amine

Trimethylsilyl acetylene

→

2-(trimethylsilylethynyl)-4,6-difluoro-N-carbethoxyaniline

Rendimiento 71.0%

Disolventes

CH3CN

Condiciones de reacción

Tratamiento posterior

1. 1
   Otropurged with N2
2. 2
   workup.ADDITIONare added
3. 3
   Lavadorinsed in with 100 mL of CH3CN
4. 4
   Otroreaction
5. 5
   Temperaturais refluxed under N2
6. 6
   OtroApproximately 2 hours later, the starting material is consumed
7. 7
   TemperaturaThe reaction is cooled
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated
10. 10
    workup.DISSOLUTIONthe residue is dissolved in ethyl acetate
11. 11
    Lavadowashed with H2O, brine
12. 12
    Secadodried (Na2SO4)
13. 13
    Filtraciónfiltered
14. 14
    Concentraciónconcentrated
15. 15
    Otrois purified by flash chromatography (SiO2, ethyl acetate/hexane gradient)

Procedimiento

In a 2 L flask, 2-bromo-4,6-difluoro-N-carbethoxy aniline (42 g, 150 mmol) in CH3CN (500 mL) is degassed with vacuum and purged with N2. Dichlorobis(triphenylphosphine)palladium(II) (10.5 g, 15 mmol, 10 mol %), followed by CuI (710 mg, 4 mmol, 2.5 mol %) and triethyl amine (41 mL) are added and rinsed in with 100 mL of CH3CN. Trimethylsilyl acetylene (31.8 ml, 225 mmol) is added and reaction is refluxed under N2. Approximately 2 hours later, the starting material is consumed, indicated by TLC (20% ethyl acetate/hexane, UV). The reaction is cooled, filtered, concentrated, and the residue is dissolved in ethyl acetate, washed with H2O, brine, dried (Na2SO4), filtered, concentrated, and is purified by flash chromatography (SiO2, ethyl acetate/hexane gradient) to yield 30 g of 2-(trimethylsilylethynyl)-4,6-difluoro-N-carbethoxyaniline (71%).

Fuente