Cesium carbonate → Tert-butyl 4-(2-(ethoxycarbonyl)-4-methylbenzofuran-5-yl)piperazine-1-carboxylate

HRID 2036046Notes

Reaction equation

HRID 2036046 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].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.[CH2:53]([O:55][C:56]([C:58]1[O:59][C:60]2[CH:66]=[CH:65][C:64](Br)=[C:63]([CH3:68])[C:61]=2[CH:62]=1)=[O:57])[CH3:54].[C:69]([O:73][C:74]([N:76]1[CH2:81][CH2:80][NH:79][CH2:78][CH2:77]1)=[O:75])([CH3:72])([CH3:71])[CH3:70]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.CCCCCC.C1(C)C=CC=CC=1>[C:69]([O:73][C:74]([N:76]1[CH2:81][CH2:80][N:79]([C:64]2[CH:65]=[CH:66][C:60]3[O:59][C:58]([C:56]([O:55][CH2:53][CH3:54])=[O:57])=[CH:62][C:61]=3[C:63]=2[CH3:68])[CH2:78][CH2:77]1)=[O:75])([CH3:72])([CH3:70])[CH3:71]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 67200885Ethyl 5-bromo-4-methylbenzofuran-2-carboxylate

Product 1

HCID 67201242Tert-butyl 4-(2-(ethoxycarbonyl)-4-methylbenzofuran-5-yl)piperazine-1-carboxylateYield 360.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Toluene (30 ml) was stirred under argon atmosphere for 30 minutes at room temperature. Cesium carbonate (4.83 g, 0.015 mol), palladium acetate (0.19 g, 0.0008 mol), BINAP (0.66 g, 0.001 mol), 5-Bromo-4-methyl-benzofuran-2-carboxylic acid ethyl ester (3 g, 0.010 mol) and piperazine-1-carboxylic acid tert-butyl ester (2.16 g, 0.001 mol) was added with a regular interval of 30 minutes under argon atmosphere. The reaction mixture was stirred for 30 minutes at room temperature and then heated to reflux. The mixture was maintained at reflux for 16 hours. The reaction mixture was diluted with ethyl acetate (50 ml) and the inorganic material was filtered. The filtrate was then washed with water (2×15 ml), brine solution (50 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude product as dark brown solid. Column chromatography using 5/95 ethyl acetate/hexane yielded 4-(2-ethoxycarbonyl-4-methyl-benzofuran-5-yl)-piperazine-1-carboxylic acid tert-butyl ester (1.4 g, 34.1%)

Workup

  1. temperatureheated to reflux
  2. temperatureThe mixture was maintained
  3. temperatureat reflux for 16 hours
  4. filtrationthe inorganic material was filtered
  5. washThe filtrate was then washed with water (2×15 ml), brine solution (50 ml)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto get crude product as dark brown solid

Sources & evidence

ORD record
ord-2e7eb1dcac4e472b84af54c7f112460e
Source dataset
uspto-grants-2013_11
Patent number
US08575161B2

Reaction notes

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