Citric Acid → HCID 68959346, compound

HRID 2191774Notes

Reaction equation

HRID 2191774 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[C:4]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:3]=1.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>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].C1(C)C=CC=CC=1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:4]2[CH:3]=[C:2]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24]3)[CH:14]=[CH:13][C:5]=2[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:17][CH:18]=1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 798IndoleHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl3×HCID 44558591Tri-t-butylphosphine fluoroborate3×HCID 68956988Tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate

Product 1

HCID 68959346HCID 68959346, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst3×HCID 1140TolueneSolvent2×

Procedure

To toluene 3.0 mL solution of tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate 0.10 g were added 1H-indole 48 mq, tripotassium phosphate 0.12 g, tris(dibenzylideneacetone)dipalladium(0) 8.0 mg, tri-tert-butylphosphine tetrafluoroborate 2.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 7.0 mg at room temperature, and it was heated and refluxed for 2 hours. After the reaction mixture was cooled to room temperature, tris(dibenzylideneacetone)dipalladium(0) 8.0 mg, tri-tert-butylphosphine tetrafluoroborate 2.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 7.0 mg were added to it, and it was heated and refluxed for 3 hours. After the reaction mixture was cooled to room temperature, tris(dibenzylideneacetone)dipalladium(0) 8.0 mg, tri-tert-butylphosphine tetrafluoroborate 2.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 7.0 mg were added to it, and it was heated and refluxed for 7 hours. After the reaction mixture was cooled to room temperature, toluene and 10% citric acid aqueous solution were added. 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=5:1] to give tert-butyl 2-(4-fluoroanilino)-4-(1H-indol-1-yl)benzoate.

Workup

  1. temperatureit was heated
  2. temperaturerefluxed for 2 hours
  3. temperaturewas heated
  4. temperaturerefluxed for 3 hours
  5. temperatureAfter the reaction mixture was cooled to room temperature
  6. temperaturewas heated
  7. temperaturerefluxed for 7 hours
  8. temperatureAfter the reaction mixture was cooled to room temperature
  9. customThe organic layer was separated
  10. washafter sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c2eae77d798a42aebfb7391a3678d5d0
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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