Citric Acid → HCID 67343160, compound

HRID 1673511Notes

Reaction equation

HRID 1673511 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:16]([NH:24][C:25]1[CH:37]=[C:36](Br)[CH:35]=[CH:34][C:26]=1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].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].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(OCC)(=O)C.C1(C)C=CC=CC=1>[C:16]([NH:24][C:25]1[CH:37]=[C:36]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[CH:35]=[CH:34][C:26]=1[C:27]([O:29][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:28])(=[O:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

11

Reactant 5

HCID 311Citric AcidHCID 798Indole2×HCID 10796Cesium carbonateHCID 62657Potassium Phosphate, TribasicHCID 67343005Tert-butyl 2-(benzamido)-4-bromobenzoate

Product 1

HCID 67343160HCID 67343160, compoundYield 58.6%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst2×HCID 44558591Tri-t-butylphosphine fluoroborateCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

33 mg of 1H-indole, 0.12 g of cesium carbonate, 5.1 mg of tris(dibenzylideneacetone)dipalladium(0), 1.6 mg of tri-tert-butylphosphine tetrafluoroborate and 4.4 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl were added to 1.4 mL of toluene solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate at room temperature, and the resulting mixture was heated to reflux under nitrogen atmosphere for 4 hours. After the reaction mixture was cooled to room temperature, 33 mg of 1H-indole, 79 mg of tripotassium phosphate, 5.1 mg of tris(dibenzylideneacetone)dipalladium(0), 1.6 mg of tri-tert-butylphosphine tetrafluoroborate and 4.4 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 4 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added and insoluble were removed by filtration. The organic layer was separated, and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane:ethyl acetate=20:1] to obtain 45 mg of tert-butyl 2-(benzamido)-4-(1H-indol-1-yl)benzoate as colorless oil.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux under nitrogen atmosphere for 4 hours
  3. temperaturethe resulting mixture was heated
  4. temperatureto reflux under nitrogen atmosphere for 4 hours
  5. temperatureAfter the reaction mixture was cooled to room temperature
  6. custominsoluble were removed by filtration
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous magnesium sulfate
  9. washafter washed with a saturated sodium chloride aqueous solution
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane:ethyl acetate=20:1]

Sources & evidence

ORD record
ord-daf4f514ea124e2a8235c8a20d367ea5
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Reaction notes

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