Reacción #450956

Ecuación de reacción

2-amino-5-ethynyl-6-methylbenzonitrile

4-trifluoromethylphenyl iodide

triethylamine

iodide

→

2-amino-6-methyl-5-[(4-trifluoromethylphenyl)ethynyl]benzonitrile

Rendimiento 72.7%

Disolventes

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónAfter this time the reaction mixture was concentrated under reduced pressure to a residue
2. 2
   OtroThe residue was partitioned between ethyl acetate and aqueous 1N hydrochloric acid
3. 3
   FiltraciónThe two-layered mixture was filtered
4. 4
   Otroto remove a solid
5. 5
   OtroThe aqueous layer and the organic layer were separated
6. 6
   Lavadothe aqueous layer was washed with ethyl acetate
7. 7
   LavadoThe ethyl acetate wash
8. 8
   Lavadothe combination was washed with an aqueous solution of 10% lithium chloride
9. 9
   SecadoThe organic layer was dried with magnesium sulfate
10. 10
    Filtraciónfiltered
11. 11
    ConcentraciónThe filtrate was concentrated under reduced pressure to a residue
12. 12
    OtroThe residue was triturated with methylene chloride
13. 13
    Filtraciónfiltered
14. 14
    LavadoElution
15. 15
    Concentraciónconcentrated under reduced pressure

Procedimiento

A solution of 3.5 grams (0.022 mole) of 2-amino-5-ethynyl-6-methylbenzonitrile, 8.4 grams (0.031 mole) of 4-trifluoromethylphenyl iodide, 10.7 grams (0.077 mole) of triethylamine, 0.5 gram (catalyst) of bis(triphenylphosphine)palladium(II) chloride, and 0.5 gram (catalyst) of copper(l) iodide in 100 mL of acetonitrile was stirred at ambient temperature for about 18 hours. After this time the reaction mixture was concentrated under reduced pressure to a residue. The residue was partitioned between ethyl acetate and aqueous 1N hydrochloric acid. The two-layered mixture was filtered to remove a solid. The aqueous layer and the organic layer were separated, and the aqueous layer was washed with ethyl acetate. The ethyl acetate wash was combined with the organic layer, and the combination was washed with an aqueous solution of 10% lithium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was triturated with methylene chloride and filtered. The filtrate was subjected to column chromatography on silica gel. Elution was accomplished using methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 4.8 grams of 2-amino-6-methyl-5-[(4-trifluoromethylphenyl)ethynyl]benzonitrile, mp 136°-138° C. The NMR spectrum was consistent with the proposed structure.

Fuente