Citric Acid → HCID 58508797, compound

HRID 454782Notes

Reaction equation

HRID 454782 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:48]1[CH:60]=[CH:59][C:51]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])=[C:50]([NH:61][C:62]([C:64]2[CH:65]=[N:66][CH:67]=[C:68]([C:70]3[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=3)[CH:69]=2)=[O:63])[CH:49]=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>[O:10]1[CH2:11][CH2:12][N:7]([C:48]2[CH:60]=[CH:59][C:51]([C:52]([O:54][C:55]([CH3:57])([CH3:56])[CH3:58])=[O:53])=[C:50]([NH:61][C:62]([C:64]3[CH:65]=[N:66][CH:67]=[C:68]([C:70]4[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=4)[CH:69]=3)=[O:63])[CH:49]=2)[CH2:8][CH2:9]1

Participants

10

Reactant 5

HCID 311Citric AcidHCID 8083Morpholine3×HCID 10796Cesium carbonate2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 58508430Tert-butyl 4-bromo-2-(5-phenylpyridine-3-carboxamido)benzoate

Product 1

HCID 58508797HCID 58508797, compound

Reagents, catalysts & solvents 4

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

Procedure

Cesium carbonate (0.14 g), morpholine (0.029 mL), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (5 mg), tris(dibenzylideneacetone)dipalladium(0) (2 mg), and palladium(II) acetate (1 mg) were added to a toluene (3.0 mL) solution of tert-butyl 4-bromo-2-(5-phenylpyridine-3-carboxamido)benzoate (0.10 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour. The reaction mixture was cooled to room temperature, and then morpholine (0.029 mL) was added thereto, followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then cesium carbonate (72 mg), morpholine (0.029 mL), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (5 mg), tris(dibenzylideneacetone)dipalladium(0) (2 mg), and palladium(II) acetate (1 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 4 hours. The reaction mixture was cooled to room temperature, and then ethyl acetate and a 10% aqueous solution of citric acid were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 85-70% hexane/ethyl acetate] to obtain tert-butyl 4-morpholino-2-(5-phenylpyridine-3-carboxamido)benzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 2 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. temperatureby heating
  7. temperatureto reflux under a nitrogen atmosphere for 4 hours
  8. temperatureThe reaction mixture was cooled to room temperature
  9. customThe organic layer was separated
  10. washwashed with a saturated aqueous solution of sodium chloride
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography [eluent: 85-70% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-768bb755152d4066bf6f584054a18db0
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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