Cesium carbonate → Ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate

HRID 1471671Notes

Reaction equation

HRID 1471671 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:42]1[C:47]2[CH:48]=[C:49]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[O:50][C:46]=2[CH:45]=[CH:44][CH:43]=1.[CH2:56]([N:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>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]>[CH2:56]([N:63]1[CH2:68][CH2:67][N:66]([C:42]2[C:47]3[CH:48]=[C:49]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[O:50][C:46]=3[CH:45]=[CH:44][CH:43]=2)[CH2:65][CH2:64]1)[C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 759941-BenzylpiperazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67983046Ethyl 4-chlorobenzofuran-2-carboxylate

Product 1

HCID 67982691Ethyl 4-(4-benzylpiperazin-1-yl)benzofuran-2-carboxylate

Reagents, catalysts & solvents 2

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

Procedure

X-Phos (1.1 g, 2.2 mmol.), Pd2(dba)3 (1.0 g, 1.1 mmol) and cesium carbonate (14.5 g, 44 mmol) were added to a degassed solution of ethyl 4-chlorobenzofuran-2-carboxylate (Example 1b), 5.0 g, 22 mmol) and benzylpiperazine (5.8 ml, 33 mmol) in dioxane (100 mL). The reaction mixture was heated to +110° C. for 3 h, cooled to room temperature, filtered through a short pad of Celite and the filtrate was concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography by using hexane/ethyl acetate (3/1) as eluant to give the title compound. Yield: 7.0 g (86%). 1H NMR (400 MHz, CDCl3) δ ppm 1.43 (t, 3H) 2.69 (m, 4H) 3.28 (m, 4H) 4.46 (q, 2H) 6.68 (d, 1H) 7.20-7.43 (m, 7H) 7.59 (s, 1H).

Workup

  1. temperatureThe reaction mixture was heated to +110° C. for 3 h
  2. filtrationfiltered through a short pad of Celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe crude residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-dacc73c9c5b74f2390d103ed9a1ee9ba
Source dataset
uspto-grants-2015_04
Patent number
US09012457B2

Reaction notes

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