Citric Acid → Benzyl 2-(benzyloxy)-3-(pyridin-3-yl)benzoate

HRID 454477Notes

Reaction equation

HRID 454477 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:24]([O:31][C:32]1[C:47](Cl)=[CH:46][CH:45]=[CH:44][C:33]=1[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=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>[CH2:24]([O:31][C:32]1[C:47]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[CH:46][CH:45]=[CH:44][C:33]=1[C:34]([O:36][CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:35])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

9

Reactant 4

HCID 311Citric AcidHCID 62657Potassium Phosphate, Tribasic2×HCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine2×HCID 66990653Benzyl 2-(benzyloxy)-3-chlorobenzoate

Product 1

HCID 66990338Benzyl 2-(benzyloxy)-3-(pyridin-3-yl)benzoateYield 89.2%

Reagents, catalysts & solvents 4

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

Procedure

3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridine (0.25 g), tripotassium phosphate (0.47 g), palladium(II) acetate (4.5 mg), and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (4.1 mg) were added to a toluene (5.3 mL) solution of the obtained benzyl 2-(benzyloxy)-3-chlorobenzoate (0.35 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour and 40 minutes. The reaction mixture was cooled to room temperature, and then 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.12 g), tripotassium phosphate (0.23 g), palladium(II) acetate (4.5 mg), and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (4.1 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 3 hours. After cooling the reaction mixture to room temperature, a 10% aqueous solution of citric acid and ethyl acetate were added thereto, and 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: 90-65% hexane/ethyl acetate] to obtain 0.35 g of benzyl 2-(benzyloxy)-3-(pyridin-3-yl)benzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour and 40 minutes
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 3 hours
  5. temperatureAfter cooling the reaction mixture 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: 90-65% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-181482bd86914e2c99641522378ca2aa
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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