Реакция #450956

Уравнение реакции

2-amino-5-ethynyl-6-methylbenzonitrile

4-trifluoromethylphenyl iodide

triethylamine

iodide

→

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

Выход 72.7%

Растворители

acetonitrile

Условия реакции

Обработка

1. 1
   КонцентрированиеAfter this time the reaction mixture was concentrated under reduced pressure to a residue
2. 2
   ДругоеThe residue was partitioned between ethyl acetate and aqueous 1N hydrochloric acid
3. 3
   ФильтрацияThe two-layered mixture was filtered
4. 4
   Другоеto remove a solid
5. 5
   ДругоеThe aqueous layer and the organic layer were separated
6. 6
   Промывкаthe aqueous layer was washed with ethyl acetate
7. 7
   ПромывкаThe ethyl acetate wash
8. 8
   Промывкаthe combination was washed with an aqueous solution of 10% lithium chloride
9. 9
   СушкаThe organic layer was dried with magnesium sulfate
10. 10
    Фильтрацияfiltered
11. 11
    КонцентрированиеThe filtrate was concentrated under reduced pressure to a residue
12. 12
    ДругоеThe residue was triturated with methylene chloride
13. 13
    Фильтрацияfiltered
14. 14
    ПромывкаElution
15. 15
    Концентрированиеconcentrated under reduced pressure

Методика

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.

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