Citric Acid → HCID 67343098, compound

HRID 1673565Notes

Reaction equation

HRID 1673565 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.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.[C:53]([NH:61][C:62]1[CH:74]=[C:73](Br)[CH:72]=[CH:71][C:63]=1[C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])(=[O:60])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>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([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:53]([NH:61][C:62]1[CH:74]=[C:73]([N:10]2[CH2:9][CH2:8][CH:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:12][CH2:11]2)[CH:72]=[CH:71][C:63]=1[C:64]([O:66][C:67]([CH3:69])([CH3:70])[CH3:68])=[O:65])(=[O:60])[C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1

Participants

10

Reactant 5

HCID 311Citric AcidHCID 10796Cesium carbonateHCID 698734-PhenylpiperidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 67343005Tert-butyl 2-(benzamido)-4-bromobenzoate

Product 1

HCID 67343098HCID 67343098, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

86 mg of 4-phenylpiperidine, 0.22 g of cesium carbonate, 2.4 mg of tris(dibenzylideneacetone)dipalladium(0), 1.2 mg of palladium acetate and 6.3 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl were added to 3.0 mL of toluene solution containing 0.10 g of tert-butyl 2-(benzamido)-4-bromobenzoate, and the resulting mixture was heated to reflux for 2 hours. After the reaction mixture was cooled to room temperature, 2.4 mg of tris(dibenzylideneacetone)dipalladium(0), 1.2 mg of palladium acetate and 6.3 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl were added and the resulting mixture was heated to reflux for 6 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane:ethyl acetate=10:1] to obtain tert-butyl 2-(benzamido)-4-(4-phenylpiperidin-1-yl)benzoate as pale yellow solid.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 2 hours
  3. temperaturethe resulting mixture was heated
  4. temperatureto reflux for 6 hours
  5. temperatureAfter the reaction mixture was cooled to room temperature
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous magnesium sulfate
  8. washafter washed with a saturated sodium chloride aqueous solution
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane:ethyl acetate=10:1]

Sources & evidence

ORD record
ord-51665185760c4980a144e588644e73c2
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Reaction notes

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