4-Bromoaniline → HCID 178511966, compound

HRID 1466422Notes

Reaction equation

HRID 1466422 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.C[Al](C)C.[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:15]=1[C:16]#[N:17]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.CO>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:16](=[NH:17])[C:15]2[C:14]([F:13])=[CH:21][CH:20]=[CH:19][C:18]=2[F:22])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 78074-BromoanilineHCID 746952,6-DifluorobenzonitrileHCID 16682925Trimethylaluminum

Product 1

HCID 178511966HCID 178511966, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

4-bromoaniline (1.72 g, 10 mmol) was placed into a three-neck reactor, and the reactor was flushed with argon for 20 min. 50 mL anhydrous toluene was added. After cooling to 0° C., trimethylaluminum (7.5 mL, 2.0M solution in toluene, 15 mmol) was added slowly to keep the inner temperature below 18° C. After addition, the reaction mixture was warmed to room temperature and then stirred for additional 2 hrs. A solution of 2,6-difluorobenzonitrile (2.78 g, 20 mmol) in 50 mL anhydrous toluene was added, and the reaction mixture was heated to 80° C. After 18 hrs, the reaction mixture was cooled to room temperature and poured over a slurry of silica gel in CHCl3/MeOH (4/1, VAT). After being stirring for 20 min, the mixture was filtered and the residue was washed with a mixture of CHCl3/MeOH (4/1, V/V). The combined filtrates were concentrated in vacuo, and the resulting solid was stirred with a solution of Hexane/Ether (3/1, V/V). The intermediate was filtered and washed with additional Hexane/Ether (3/1, V/V) to give a white solid (2.4 g, 79% yield), which was used directly for the next step without further purification.

Workup

  1. customthe reactor was flushed with argon for 20 min
  2. addition50 mL anhydrous toluene was added
  3. customthe inner temperature below 18° C
  4. additionAfter addition
  5. temperaturethe reaction mixture was warmed to room temperature
  6. temperaturethe reaction mixture was heated to 80° C
  7. waitAfter 18 hrs
  8. temperaturethe reaction mixture was cooled to room temperature
  9. stirringAfter being stirring for 20 min
  10. filtrationthe mixture was filtered
  11. washthe residue was washed with a mixture of CHCl3/MeOH (4/1, V/V)
  12. concentrationThe combined filtrates were concentrated in vacuo
  13. stirringthe resulting solid was stirred with a solution of Hexane/Ether (3/1, V/V)
  14. filtrationThe intermediate was filtered
  15. washwashed with additional Hexane/Ether (3/1, V/V)

Sources & evidence

ORD record
ord-4406da61b50e47be904ce88de0c4050f
Source dataset
uspto-grants-2015_04
Patent number
US09000022B2

Reaction notes

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