Cesium carbonate → Ethyl-7-(4-Benzyl-piperazin-1-yl)-5-fluorobenzofuran-2-carboxylate

HRID 535677

Reaction equation

HRID 535677 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:66]([O:68][C:69]([C:71]1[O:72][C:73]2[C:79](Br)=[CH:78][C:77]([F:81])=[CH:76][C:74]=2[CH:75]=1)=[O:70])[CH3:67]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:66]([O:68][C:69]([C:71]1[O:72][C:73]2[C:79]([N:11]3[CH2:12][CH2:13][N:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:9][CH2:10]3)=[CH:78][C:77]([F:81])=[CH:76][C:74]=2[CH:75]=1)=[O:70])[CH3:67]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 759941-BenzylpiperazineHCID 634876Binap, (A+-)-HCID 59636759Ethyl 7-bromo-5-fluorobenzofuran-2-carboxylate

Product 1

HCID 59636706Ethyl-7-(4-Benzyl-piperazin-1-yl)-5-fluorobenzofuran-2-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Benzylpiperazine (1.3 mL, 8.4 mmol), BINAP (0.43 g, 0.69 mmol), Pd2 dba3 (0.32 g, 0.35 mmol), cesium carbonate (3.25 g, 9.76 mmol) were added to a degassed solution of 7-bromo-5-fluoro-benzofuran-2-carboxylic acid ethyl ester (2.0 g, 6.97 mmol) in toluene (50 mL). The mixture was heated at reflux over night. After cooling, the mixture was filtered through a pad of celite and washed with dichloromethane. The filtrate was concentrated under reduced pressure. The product was purified by flash chromatography (SiO2; hexane/EtOAc, 7/3). Yield: 1.6 g (60%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux over night
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered through a pad of celite
  5. washwashed with dichloromethane
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe product was purified by flash chromatography (SiO2; hexane/EtOAc, 7/3)

Sources & evidence

ORD record
ord-96e9fccfa1ad4bd3b087d99c2ad44aa4
Source dataset
uspto-grants-2014_10
Patent number
US08859534B2

Linked notes

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