2-(Trifluoromethyl)aniline → 4-[1,2,2,2-Tetrafluoro-1-(trifluoromethyl)ethyl]-2-(trifluoromethyl)benzenamine

HRID 590905Notes

Reaction equation

HRID 590905 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:9]=[CH:8][CH:7]=[CH:6][C:4]=1[NH2:5].S(S([O-])=O)([O-])=O.[Na+].[Na+].C(=O)([O-])O.[Na+].[F:25][C:26]([F:35])([F:34])[C:27](I)([F:32])[C:28]([F:31])([F:30])[F:29]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O.C(OCC)(=O)C>[F:25][C:26]([F:35])([F:34])[C:27]([F:32])([C:8]1[CH:7]=[CH:6][C:4]([NH2:5])=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:9]=1)[C:28]([F:31])([F:30])[F:29]

Participants

8

Reactant 4

HCID 69222-(Trifluoromethyl)anilineHCID 24489Sodium DithioniteHCID 33978Perfluoroisopropyl iodideHCID 516892Sodium Bicarbonate

Product 1

HCID 582974594-[1,2,2,2-Tetrafluoro-1-(trifluoromethyl)ethyl]-2-(trifluoromethyl)benzenamineYield 30%

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

100 g (0.608 mol) of 2-(trifluoromethyl)aniline, 131 g (0.639 mol) of 85% sodium hydrosulfite, and 20.9 g (0.0608 mol) of tetrabutylammonium hydrogen sulfate were charged to a mixed solution of 1500 ml of ethyl acetate and 1500 ml of water, and 53.9 g (0.639 mol) of sodium hydrogen carbonate was added thereto. 198 g (0.669 mol) of heptafluoroisopropyl iodide was added dropwise thereto at room temperature, followed by stirring at room temperature for 6 hours. After the liquid separation, the solvent of the organic layer was evaporated under reduced pressure, and 500 ml of ethyl acetate was charged thereto. 160 g (0.608 mol) of a 4 M hydrogen chloride/ethyl acetate solution was added dropwise thereto, followed by stirring at room temperature for 30 minutes, and then stirring at 5° C. for 1 hour. After the filtration, the filtrate was washed with water and a saturated aqueous sodium hydrogen carbonate in this order, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent solvent; hexane:ethyl acetate=10:1) to prepare 60.0 g (yield 30%) of a target compound.

Workup

  1. additionwas added
  2. customat room temperature
  3. customAfter the liquid separation
  4. customthe solvent of the organic layer was evaporated under reduced pressure, and 500 ml of ethyl acetate
  5. additionwas charged
  6. addition160 g (0.608 mol) of a 4 M hydrogen chloride/ethyl acetate solution was added dropwise
  7. stirringby stirring at room temperature for 30 minutes
  8. stirringstirring at 5° C. for 1 hour
  9. filtrationAfter the filtration
  10. washthe filtrate was washed with water
  11. dry with materiala saturated aqueous sodium hydrogen carbonate in this order, and then dried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (eluent solvent; hexane:ethyl acetate=10:1)

Sources & evidence

ORD record
ord-f354781dd2fa4fa98e822ce28402d5d3
Source dataset
uspto-grants-2016_01
Patent number
US09237745B2

Reaction notes

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