Hydrochloric Acid → (2-Chloro-6-fluorophenyl)-P-tolyl-amine

HRID 382504Notes

Reaction equation

HRID 382504 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].Br[C:62]1[C:67]([F:68])=[CH:66][CH:65]=[CH:64][C:63]=1[Cl:69].Cl>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:69][C:63]1[CH:64]=[CH:65][CH:66]=[C:67]([F:68])[C:62]=1[NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7813p-ToluidineHCID 634876Binap, (A+-)-HCID 219386602-Bromo-1-chloro-3-fluorobenzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 21100364(2-Chloro-6-fluorophenyl)-P-tolyl-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 146.1 g (1.36 mol) of p-toluidine, 12.6 g (0.02 mol) of (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 261.9 g (2.73 mol) of sodium t-butoxide, 314.1 g (1.50 mol) of 2-bromo-3-fluoro-chlorobenzene and 6.3 g (0.0069 mol) of tris(dibenzylideneacetone)dipalladium(0) in 3000 ml of toluene is heated to 110° over 30 minutes and stirred an additional 4 hours at this temperature. The mixture is cooled to room temperature and a solution of 680 ml 37% hydrochloric acid and 680 ml of water is added over 15 minutes. The mixture is stirred for 20 minutes and filtered through a pad of Celite. The layers are separated and the organic phase is washed twice with 680 ml of water and once with a solution of 225 g of sodium chloride in 680 ml of water. The solvents are evaporated under reduced pressure to give N-(2′-chloro-6′-fluorophenyl)-4-methylaniline as an oil, b.p. 129-131°/0.5 mm Hg.

Workup

  1. temperatureis heated to 110° over 30 minutes
  2. stirringThe mixture is stirred for 20 minutes
  3. filtrationfiltered through a pad of Celite
  4. customThe layers are separated
  5. washthe organic phase is washed twice with 680 ml of water and once with a solution of 225 g of sodium chloride in 680 ml of water
  6. customThe solvents are evaporated under reduced pressure

Sources & evidence

ORD record
ord-7217a856ac394162acba3a03aaf6d4f1
Source dataset
uspto-grants-2001_10
Patent number
US06310099B1

Reaction notes

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