Toluene → 2-Amino-6-methyl-5-(3-fluoro-5-trifluoromethylphenyl)benzonitrile

HRID 1734607Notes

Reaction equation

HRID 1734607 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:7](Br)=[C:6]([CH3:11])[C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1.[F:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([C:28]2[CH:29]=[C:30]([C:32]([F:34])([F:33])[F:35])[CH:31]=[C:26]([F:25])[CH:27]=2)=[C:6]([CH3:11])[C:3]=1[C:4]#[N:5]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27831923-Fluoro-5-(trifluoromethyl)benzeneboronic acidHCID 224657376-Amino-3-bromo-2-methylbenzonitrile

Product 1

HCID 545688402-Amino-6-methyl-5-(3-fluoro-5-trifluoromethylphenyl)benzonitrileYield 103%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Under a dry nitrogen atmosphere, 0.5 gram (0.0004 mole) of tetrakis(triphenylphosphine)palladium(0) was added to a stirred mixture of 2.8 grams (0.0132 mole) of 2-amino-5-bromo-6-methylbenzonitrile (prepared as in Step C of Example 1), 35 mL of aqueous 2M sodium carbonate and 50 mL of toluene. To this was then added dropwise a solution of 3.3 grams (0.0159 mole) of 3-fluoro-5-trifluoromethylphenylboronic acid in 10 mL of ethanol. Upon completion of addition, the reaction mixture was warmed to about 80° C., where it was stirred for seven hours. After this time the reaction mixture was poured into 200 mL of water. The mixture was then extracted with four 100 mL portions of ethyl acetate. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished with methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 4.0 grams of 2-amino-6-methyl-5-(3-fluoro-5-trifluoromethylphenyl)benzonitrile, mp 96°-97° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. extractionThe mixture was then extracted with four 100 mL portions of ethyl acetate
  3. dry with materialThe combined extracts were dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure to a residue
  6. washElution
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-36e7851f31f540eab3e5b750ffdf9278
Source dataset
uspto-grants-1996_07
Patent number
US05534518

Reaction notes

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