Citric Acid → HCID 68964088, compound

HRID 2191793Notes

Reaction equation

HRID 2191793 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.Br[C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=1.C(N(CCCC)CCCC)CCC.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:26]=[CH:27][C:28]([O:31][C:32]([F:33])([F:34])[F:35])=[CH:29][CH:30]=3)[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

8

Reactant 4

HCID 311Citric AcidHCID 7622Tributylamine2×HCID 5210081-Bromo-4-(trifluoromethoxy)benzene2×HCID 68959213Tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate

Product 1

HCID 68964088HCID 68964088, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

To N,N-dimethylacetamide 3.0 mL solution of tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate 0.10 g were added 1-bromo-4-(trifluoromethoxy)benzene 0.12 g, tributylamine 0.15 mL and palladium acetate 3.6 mg at room temperature, and it was stirred at 110° C. for 6 hours. Palladium acetate 3.6 mg was added to it, and it was stirred at 130° C. for 6 hours. 1-bromo-4-(trifluoromethoxy)benzene 0.12 g, tributylamine 0.076 mL and (E)-di(μ-acetato)bis(o-(di-o-tolylphosphino)benzyl)dipalladium(II) 6.3 mg were added to it, and it was stirred at 80° C. for 2 hours. 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, and the solvent was removed under reduced pressure after sequential washing with 10% citric acid aqueous solution, saturated sodium thiosulfate aqueous solution and saturated sodium chloride aqueous solution. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008, eluent; hexane:ethyl acetate=10:1] to give tert-butyl 2-(4-fluoroanilino)-4-((E)-2-(4-(trifluoromethoxy)phenyl)vinyl)benzoate.

Workup

  1. stirringwas stirred at 130° C. for 6 hours
  2. stirringwas stirred at 80° C. for 2 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. customThe organic layer was separated
  5. customcollected
  6. customthe solvent was removed under reduced pressure
  7. washafter sequential washing with 10% citric acid aqueous solution, saturated sodium thiosulfate aqueous solution and saturated sodium chloride aqueous solution

Sources & evidence

ORD record
ord-4d7f93a7a3a440db837f458fe8c2055b
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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