Citric Acid → Tert-butyl 2-(benzamido)-4-(2,4-dichlorophenoxy)benzoate

HRID 1673563

Reaction equation

HRID 1673563 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].[H-].[Na+].[C:12]([NH:20][C:21]1[CH:33]=[C:32](Br)[CH:31]=[CH:30][C:22]=1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.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(OCC)(=O)C.C1(C)C=CC=CC=1>[C:12]([NH:20][C:21]1[CH:33]=[C:32]([O:9][C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[CH:31]=[CH:30][C:22]=1[C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])(=[O:19])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 84492,4-Dichlorophenol2×HCID 24758Sodium hydride2×HCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 67343005HCID 67343005, compound

Product 1

HCID 67342198Tert-butyl 2-(benzamido)-4-(2,4-dichlorophenoxy)benzoate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

91 mg of 2,4-dichlorophenol was added to 2.1 mL of toluene suspension containing 22 mg of 60% sodium hydride at room temperature, and the resulting mixture was heated to reflux under nitrogen atmosphere for 15 minutes. After the reaction mixture was cooled to room temperature, 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate, 4.7 mg of 2-(di-tert-butylphosphine)-2′,4′,6′-triisopropylbiphenyl and 6.8 mg of tris(dibenzylideneacetone)dipalladium(0) were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 6 hours. After the reaction mixture was cooled to room temperature, 61 mg of 2,4-dichlorophenol, 15 mg of 60% sodium hydride, 4.7 mg of 2-(di-tert-butylphosphino)-2′, 4′,6′-triisopropylbiphenyl and 6.8 mg of tris(dibenzylideneacetone)dipalladium(0) were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 10 hours. After the reaction mixture was cooled to room temperature, 10% citric acid aqueous solution and ethyl acetate were added and insoluble were removed by filtration. 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=20:1] to obtain tert-butyl 2-(benzamido)-4-(2,4-dichlorophenoxy)benzoate.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux under nitrogen atmosphere for 15 minutes
  3. temperaturethe resulting mixture was heated
  4. temperatureto reflux under nitrogen atmosphere for 6 hours
  5. temperatureAfter the reaction mixture was cooled to room temperature
  6. temperaturethe resulting mixture was heated
  7. temperatureto reflux under nitrogen atmosphere for 10 hours
  8. temperatureAfter the reaction mixture was cooled to room temperature
  9. custominsoluble were removed by filtration
  10. customThe organic layer was separated
  11. dry with materialdried over anhydrous magnesium sulfate
  12. washafter washed with a saturated, sodium chloride aqueous solution
  13. customthe solvent was evaporated under reduced pressure
  14. customThe obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane; ethyl acetate=20:1]

Sources & evidence

ORD record
ord-190cf9f47dee4958835978e181a26b08
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Linked notes

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