Bromobenzene → 2-chloro-4-fluoro-N-phenylaniline

HRID 879912Notes

Reaction equation

HRID 879912 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].Br[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1C=CC=CC=1C>[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH:4][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 7961BromobenzeneHCID 75013Benzenamine, 2-chloro-4-fluoro-HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 23676156Sodium t-butoxide

Product 1

HCID 860511492-chloro-4-fluoro-N-phenylanilineYield 44%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7237O-XyleneSolvent

Procedure

A mixture of 35 g (240 mmole) 2-chloro-4-fluoroaniline, 37.7 g (240 mmole) of bromobenzene, 0.6 g (12 mmole) of palladium (II)acetate, 4.8 g (24 mmole) of tri-tert-butylphosphine, 46 g (480 mmole) of sodium tert-butoxide and o-xylene 800 ml were refluxed under nitrogen for about overnight. Then, the solution was filtered at 100° C. To receive the filtrate, And the o-xylene was removed under reduced pressure from the filtrate. The filtrate was extracted with 500 ml dichloromethane and 2000 ml water, the organic layer was dried with anhydrous magnesium sulfate, the solvent was removed and the residue was purified by column chromatography on silica (hexane-ethyl acetate) to give product 23.4 g (44%).

Workup

  1. temperaturewere refluxed under nitrogen for about overnight
  2. filtrationThen, the solution was filtered at 100° C
  3. customthe o-xylene was removed under reduced pressure from the filtrate
  4. extractionThe filtrate was extracted with 500 ml dichloromethane and 2000 ml water
  5. dry with materialthe organic layer was dried with anhydrous magnesium sulfate
  6. customthe solvent was removed
  7. customthe residue was purified by column chromatography on silica (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-18d148fb42554e4b89a7bcf6d9cb2e59
Source dataset
uspto-grants-2015_03
Patent number
US08993130B2

Reaction notes

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