Cesium carbonate → Tert-butyl 4-(2,4-difluorophenyl)-2-nitrobenzoate

HRID 1673356Notes

Reaction equation

HRID 1673356 reaction equation
Cl[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1.[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C1(C)C=CC=CC=1>[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27343342,4-Difluorophenylboronic acidHCID 63896832Tert-butyl 4-chloro-2-nitrobenzoate

Product 1

HCID 67343403Tert-butyl 4-(2,4-difluorophenyl)-2-nitrobenzoateYield 48.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 1140TolueneSolvent

Procedure

To 15 mL of toluene solution containing 1.5 g of tert-butyl 4-chloro-2-nitrobenzoate, 1.1 g of 2,4-difluorophenylboronic acid, 2.3 g of cesium carbonate, 27 mg of palladium acetate and 25 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl were added sequentially, and the resulting mixture was heated to reflux under nitrogen atmosphere for 8 hours. After the reaction mixture was cooled to room temperature, insoluble were removed by filtration and added a saturated sodium hydrogen carbonate aqueous solution. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. Hexane and diisopropyl ether were added to the obtained residue and a solid substance was separated by filtration to obtain 0.95 g of tert-butyl 4-(2,4-difluorophenyl)-2-nitrobenzoate as white solid.

Workup

  1. additionwere added sequentially
  2. temperaturethe resulting mixture was heated
  3. temperatureto reflux under nitrogen atmosphere for 8 hours
  4. custominsoluble were removed by filtration
  5. additionadded a saturated sodium hydrogen carbonate aqueous solution
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous magnesium sulfate
  8. washafter washed with 10% citric acid aqueous solution
  9. customa saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure
  10. additionHexane and diisopropyl ether were added to the obtained residue
  11. customa solid substance was separated by filtration

Sources & evidence

ORD record
ord-f1b22ebecb064c74a735385689c4eec3
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Reaction notes

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