Citric Acid → Tert-butyl 4-phenyl-2-(4-phenylpyridine-2-carboxamido)benzoate

HRID 454775Notes

Reaction equation

HRID 454775 reaction equation
[C:1]1(OB=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([C:25]([NH:27][C:28]2[CH:40]=[C:39]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH:38]=[CH:37][C:29]=2[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:26])[CH:20]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:41]1([C:39]2[CH:38]=[CH:37][C:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[C:28]([NH:27][C:25]([C:21]3[CH:20]=[C:19]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH:24]=[CH:23][N:22]=3)=[O:26])[CH:40]=2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

9

Reactant 4

HCID 311Citric AcidHCID 62657Potassium Phosphate, Tribasic2×HCID 14438906HCID 14438906, compound2×HCID 58508497Tert-butyl 2-(4-chloropyridine-2-carboxamido)-4-phenylbenzoate

Product 1

HCID 58508724Tert-butyl 4-phenyl-2-(4-phenylpyridine-2-carboxamido)benzoateYield 98.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phenylboranic acid (21 mg), tripotassium phosphate (69 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.2 mg), and palladium(II) acetate (1.3 mg) were added to a toluene (1.2 mL) solution of tert-butyl 2-(4-chloropyridine-2-carboxamido)-4-phenylbenzoate (60 mg), followed by heating to reflux under a nitrogen atmosphere for 3 hours. The reaction mixture was cooled to room temperature, and then phenylboranic acid (5.4 mg), tripotassium phosphate (16 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.2 mg), and palladium(II) acetate (1.3 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 2 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 insoluble substance was removed by filtration. 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 [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 100-85% hexane/ethyl acetate] to obtain 65 mg of tert-butyl 4-phenyl-2-(4-phenylpyridine-2-carboxamido)benzoate as a colorless oily substance.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 3 hours
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 2 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customThe insoluble substance was removed by filtration
  7. customThe organic layer was separated
  8. washwashed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 100-85% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-bdee635596ce46458cb31fce7ad13748
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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