Citric Acid → tert-butyl 2-(4-fluoroanilino)-4-((E)-2-(2-methoxyphenyl)vinyl)benzoate

HRID 2191800Notes

Reaction equation

HRID 2191800 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([NH:6][C:7]2[CH:19]=[C:18]([CH:20]=[CH2:21])[CH:17]=[CH:16][C:8]=2[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:4][CH:3]=1.I[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[O:31][CH3:32].C(N(CCCC)CCCC)CCC.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.CN(C)C(=O)C>[F:1][C:2]1[CH:23]=[CH:22][C:5]([NH:6][C:7]2[CH:19]=[C:18](/[CH:20]=[CH:21]/[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[O:31][CH3:32])[CH:17]=[CH:16][C:8]=2[C:9]([O:11][C:12]([CH3:15])([CH3:13])[CH3:14])=[O:10])=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 7622TributylamineHCID 68257o-IodoanisoleHCID 44558591Tri-t-butylphosphine fluoroborateHCID 68959213Tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate

Product 1

HCID 68962915tert-butyl 2-(4-fluoroanilino)-4-((E)-2-(2-methoxyphenyl)vinyl)benzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

To N,N-dimethylacetamide 2.0 mL solution of tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate 0.10 g were added 2-iodoanisole 0.046 mL, tributylamine 0.15 mL, palladium acetate 4.0 mg and tri-tert-butylphosphine tetrafluoroborate 3.0 mg at room temperature, and it was stirred under nitrogen atmosphere at 110° C. for 1 hour and 30 minutes. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008, eluent; hexane:ethyl acetate=20:1] to give tert-butyl 2-(4-fluoroanilino)-4-((E)-2-(2-methoxyphenyl)vinyl)benzoate.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. washafter sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-fb6c67bed628447ba6a70bf63826f852
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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