Triethylamine → 2-Amino-6-methyl-5-[(4-trifluoromethylphenyl)ethynyl]benzonitrile

HRID 363774Notes

Reaction equation

HRID 363774 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]#[CH:11])=[C:6]([CH3:12])[C:3]=1[C:4]#[N:5].[F:13][C:14]([F:23])([F:22])[C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1.C(N(CC)CC)C.[I-]>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][C:18]2[CH:19]=[CH:20][C:15]([C:14]([F:23])([F:22])[F:13])=[CH:16][CH:17]=2)=[C:6]([CH3:12])[C:3]=1[C:4]#[N:5]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 30165Iodide IonHCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 540198812-Amino-5-ethynyl-6-methylbenzonitrile

Product 1

HCID 541158512-Amino-6-methyl-5-[(4-trifluoromethylphenyl)ethynyl]benzonitrileYield 72.7%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

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.

Workup

  1. concentrationAfter this time the reaction mixture was concentrated under reduced pressure to a residue
  2. customThe residue was partitioned between ethyl acetate and aqueous 1N hydrochloric acid
  3. filtrationThe two-layered mixture was filtered
  4. customto remove a solid
  5. customThe aqueous layer and the organic layer were separated
  6. washthe aqueous layer was washed with ethyl acetate
  7. washThe ethyl acetate wash
  8. washthe combination was washed with an aqueous solution of 10% lithium chloride
  9. dry with materialThe organic layer was dried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under reduced pressure to a residue
  12. customThe residue was triturated with methylene chloride
  13. filtrationfiltered
  14. washElution
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b043eb18abf04a5e96ff9d80e5ee7b48
Source dataset
uspto-grants-1999_02
Patent number
US05874579

Reaction notes

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