Citric Acid → HCID 57879483, compound

HRID 1673390Notes

Reaction equation

HRID 1673390 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:18]([NH:26][C:27]1[CH:39]=[C:38]([CH:40]=[CH2:41])[CH:37]=[CH:36][C:28]=1[C:29]([O:31]C(C)(C)C)=[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>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:18]([NH:26][C:27]1[CH:39]=[C:38]([CH2:40][CH2:41][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)[CH:37]=[CH:36][C:28]=1[C:29]([OH:31])=[O:30])(=[O:25])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 67343635Tert-butyl 2-(benzamido)-4-vinylbenzoate

Product 1

HCID 57879483HCID 57879483, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

0,087 mL of 4-bromobenzotrifluoride, 0.20 g of cesium carbonate, 30 mg of tetrabutylammonium bromide and 49 mg of polymer supported di(acetato)dicyclohexylphosphino palladium(II) were added to 2.0 mL of toluene solution containing 100 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate at room temperature and stirred at 110° C. for 48 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added. The organic layer was separated, and the solvent was evaporated under reduced pressure after washed with 10% citric acid aqueous solution. 2.4 mL of tetrahydrofuran, 0.6 mL of water, 0.42 g of sodium formate, 0.44 mL of acetic acid and 50 mg of 3.9% palladium-carbon (ethylenediamine complex) were added to the obtained residue and stirred at 50° C. for 12 hours. The reaction mixture was cooled to room temperature and ethyl acetate and 10% citric acid aqueous solution were added. The organic layer was separated and the solvent was evaporated under reduced pressure. 10 mL of trifluoroacetic acid was added to the obtained residue and stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure and the obtained residue was purified with reversed-phase silica gel column chromatography [eluent; 60-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to obtain 21 mg of 2-(benzamido)-4-(2-(4-(trifluoromethyl)phenyl)ethyl)benzoic acid as white solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. customthe solvent was evaporated under reduced pressure
  4. washafter washed with 10% citric acid aqueous solution
  5. addition2.4 mL of tetrahydrofuran, 0.6 mL of water, 0.42 g of sodium formate, 0.44 mL of acetic acid and 50 mg of 3.9% palladium-carbon (ethylenediamine complex) were added to the obtained residue
  6. stirringstirred at 50° C. for 12 hours
  7. temperatureThe reaction mixture was cooled to room temperature
  8. additionethyl acetate and 10% citric acid aqueous solution were added
  9. customThe organic layer was separated
  10. customthe solvent was evaporated under reduced pressure
  11. addition10 mL of trifluoroacetic acid was added to the obtained residue
  12. stirringstirred at room temperature for 1 hour
  13. customThe solvent was evaporated under reduced pressure
  14. customthe obtained residue was purified with reversed-phase silica gel column chromatography [eluent; 60-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution]

Sources & evidence

ORD record
ord-5f3fc0c0bf4f44eb9637bd60c3a52f65
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Reaction notes

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