4-Fluoroaniline → Methyl 2-(4-fluoroanilino)-4-methoxybenzoate

HRID 2191634Notes

Reaction equation

HRID 2191634 reaction equation
I[C:2]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(=O)([O-])[O-].[Cs+].[Cs+].[F:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.C1(C)C=CC=CC=1>[F:20][C:21]1[CH:27]=[CH:26][C:24]([NH:25][C:2]2[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:23][CH:22]=1

Participants

7

Reactant 3

HCID 97314-FluoroanilineHCID 10796Cesium carbonateHCID 54385122Methyl 2-iodo-4-methoxybenzoate

Product 1

HCID 57667822Methyl 2-(4-fluoroanilino)-4-methoxybenzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Procedure

To toluene 30 mL suspension of methyl 2-iodo-4-methoxybenzoate 2.7 g, rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl 58 mg, palladium acetate 20 mg and cesium carbonate 6.0 g was added 4-fluoroaniline 1.3 mL, and it was heated and refluxed under nitrogen atmosphere for 5 hours. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, and ethyl acetate and 1.0 mol/L hydrochloric acid were added to it. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give methyl 2-(4-fluoroanilino)-4-methoxybenzoate 2.2 g of white solid.

Workup

  1. temperaturewas heated
  2. temperaturerefluxed under nitrogen atmosphere for 5 hours
  3. filtrationinsoluble matter was filtrated
  4. additionethyl acetate and 1.0 mol/L hydrochloric acid were added to it
  5. customThe organic layer was separated
  6. washafter washing with saturated sodium chloride aqueous solution
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-ddb284a35a6946d8898ae0a176808a0e
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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