Cesium carbonate → HCID 67355976, compound

HRID 2190557Notes

Reaction equation

HRID 2190557 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1)[CH3:2].[C:18]([O:22][C:23](=[O:31])[C:24]1[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=1)([CH3:21])([CH3:20])[CH3:19].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.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]>[C:18]([O:22][C:23](=[O:31])[C:24]1[CH:29]=[CH:28][C:27]([N:14]2[CH2:13][CH2:12][N:11]([C:8]3[CH:7]=[CH:6][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:17])=[CH:10][CH:9]=3)[CH2:16][CH2:15]2)=[CH:26][CH:25]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2761178Ethyl 4-(piperazin-1-yl)benzoateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 11334366Tert-butyl 4-bromobenzoate

Product 1

HCID 67355976HCID 67355976, compoundYield 51.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed mixture of 4-(piperazin-1-yl)-benzoic acid ethyl ester (1.45 g, 6.2 mmol), 4-bromobenzoic acid tert-butyl ester (1.75 g, 6.8 mmol), cesium carbonate (3.9 g, 12 mmol) in dioxane (25 mL) was added tris(dibenzylideneacetone)dipalladium (300 mg, 5 mol %) and 2-(dicyclohexylphosphino)-2′,4′,6′-tris(isopropyl)-biphenyl (x-phos, 300 mg, 10 mol %). The mixture was heated in a sealed tube with stirring at 100° C. for 3 hrs. Solvents were evaporated and the residue was extracted with ethyl acetate and water, The organic layer was dried over sodium sulfate and solvents were evaporated. The crude material was purified through a flash column chromatography using ethyl acetate and hexanes to give the intermediate 4-[4-(4-ethoxycarbonylphenyl)-piperazin-1-yl]-benzoic acid tert-butyl ester as solid (1.3 g, 51% yield)

Workup

  1. temperatureThe mixture was heated in a sealed tube
  2. customSolvents were evaporated
  3. extractionthe residue was extracted with ethyl acetate and water
  4. dry with materialThe organic layer was dried over sodium sulfate and solvents
  5. customwere evaporated
  6. customThe crude material was purified through a flash column chromatography

Sources & evidence

ORD record
ord-c7fc89d26c95491c8ed98d35aa79d851
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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