Citric Acid → HCID 67345242, compound

HRID 1673549Notes

Reaction equation

HRID 1673549 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([F:8])[CH:7]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:18]([NH:26][C:27]1[CH:39]=[C:38](Br)[CH:37]=[CH:36][C:28]=1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=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(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:18]([NH:26][C:27]1[CH:39]=[C:38]([O:9][C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=2)[CH:37]=[CH:36][C:28]=1[C:29]([O:31][C:32]([CH3:34])([CH3:35])[CH3:33])=[O:30])(=[O:25])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

9

Reactant 4

HCID 311Citric AcidHCID 62657Potassium Phosphate, TribasicHCID 759283,5-DifluorophenolHCID 67343005Tert-butyl 2-(benzamido)-4-bromobenzoate

Product 1

HCID 67345242HCID 67345242, compoundYield 89.7%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

29 mg of 3,5-difluorophenol, 79 mg of tripotassium phosphate, 4.7 mg of 2-(di-tert-butylphosphino)-2′, 4′, 6′-triisopropylbiphenyl and 6.8 mg of tris(dibenzylideneacetone)dipalladium(0) were added to 1.4 mL of toluene solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate at room temperature, and the resulting mixture was heated to reflux under nitrogen atmosphere for 3 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution 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=10:1] to obtain 71 mg of tert-butyl 2-(benzamido)-4-(3,5-difluorophenoxy)benzoate as colorless oil.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux under nitrogen atmosphere for 3 hours
  3. custominsoluble were removed by filtration
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous magnesium sulfate
  6. washafter washed with a saturated sodium chloride aqueous solution
  7. customthe solvent was evaporated under reduced pressure
  8. 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-a526b0457a03439aadbe79e336ca251b
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Reaction notes

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