Cesium carbonate → tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate

HRID 1471672Notes

Reaction equation

HRID 1471672 reaction equation
Cl[C:2]1[C:7]2[CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[O:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[N:16]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.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]>[CH2:14]([O:13][C:11]([C:9]1[O:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([N:19]3[CH2:18][CH2:17][N:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20]3)[C:7]=2[CH:8]=1)=[O:12])[CH3:15]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67983046Ethyl 4-chlorobenzofuran-2-carboxylate

Product 1

HCID 68025136tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Ethyl 4-bromobenzofuran-2-carboxylate (prepared in analogy with ethyl 4-chlorobenzofuran-2-carboxylate, (Example 1b), starting from 2-bromo-6-hydroxy-benzaldehyde) (7.7 g, 29 mmol), tert-butyl piperazine-1-carboxylate (5.33 g, 28.6 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.31 g, 1.43 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (1.36 g, 2.86 mmol) and cesium carbonate (12.1 g, 37.2 mmol) in dioxane (40 mL) was heated under argon to +95° C. overnight. The mixture was allowed to cool, diluted with ethyl acetate and filtered through a pad of Celite. The filtrate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and eluted with 0-50% ethyl acetate in heptane. The collected fractions were combined and the solvent was removed to give the title compound, which was used in the subsequent step ii). Yield: 4.92 g, 46%. MS m/z 375.8 [M+H]+.

Workup

  1. temperatureto cool
  2. filtrationfiltered through a pad of Celite
  3. customThe filtrate was collected
  4. customthe solvent was removed by rotary evaporation
  5. additionThe crude product was added to a silica gel column
  6. washeluted with 0-50% ethyl acetate in heptane
  7. customthe solvent was removed

Sources & evidence

ORD record
ord-117d6195dd584ca184a4b65bb9b2658b
Source dataset
uspto-grants-2015_04
Patent number
US09012457B2

Reaction notes

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