Cesium carbonate → HCID 67343884, compound

HRID 1673455Notes

Reaction equation

HRID 1673455 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].[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-])O.[Na+]>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:18]([NH:26][C:27]1[CH:39]=[C:38]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])[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 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27343362,6-Difluorophenylboronic acid2×HCID 67343005Tert-butyl 2-(benzamido)-4-bromobenzoate

Product 1

HCID 67343884HCID 67343884, compoundYield 14.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst4×HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalyst4×HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

0.10 g of 2,6-difluorophenylboronic acid, 0.52 g of cesium carbonate, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl were added to 2.5 mL of toluene solution containing 0.20 g of tert-butyl 2-(benzamido)-4-bromobenzoate at room temperature sequentially, and stirred under nitrogen atmosphere at 80° C. for 1 hour and 10 minutes and then heated to reflux for 1 hour. After the reaction mixture was cooled to room temperature, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 1 hour. After the reaction mixture was cooled to room temperature, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 1 hour. After the reaction mixture was cooled to room temperature, were added 2.0 mL of toluene, 0.04 g of 2,6-difluorophenylboronic acid, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl and the resulting mixture was heated to reflux under nitrogen atmosphere for 1 hour. A saturated sodium hydrogen carbonate aqueous solution and ethyl acetate were added after the reaction mixture was cooled to room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium hydrogen carbonate aqueous solution and a saturated sodium chloride aqueous solution sequentially, 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 31 mg of tert-butyl 2-(benzamido)-4-(2,6-difluorophenyl)benzoate as white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 hour
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. temperaturethe resulting mixture was heated
  5. temperatureto reflux under nitrogen atmosphere for 1 hour
  6. temperatureAfter the reaction mixture was cooled to room temperature
  7. temperaturethe resulting mixture was heated
  8. temperatureto reflux under nitrogen atmosphere for 1 hour
  9. temperatureAfter the reaction mixture was cooled to room temperature
  10. temperaturethe resulting mixture was heated
  11. temperatureto reflux under nitrogen atmosphere for 1 hour
  12. temperaturewas cooled to room temperature
  13. customThe organic layer was separated
  14. dry with materialdried over anhydrous magnesium sulfate
  15. washafter washed with a saturated sodium hydrogen carbonate aqueous solution
  16. customa saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure
  17. 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-69c2df3719b144249eb5e945bf5440d4
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Reaction notes

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