Citric Acid → HCID 57879584, compound

HRID 1673379Notes

Reaction equation

HRID 1673379 reaction equation
[CH:1]([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)=[CH2:2].C(=O)([O-])[O-].[Cs+].[Cs+].[C:15]([NH:23][C:24]1[CH:36]=[C:35](Br)[CH:34]=[CH:33][C:25]=1[C:26]([O:28]C(C)(C)C)=[O:27])(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=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:15]([NH:23][C:24]1[CH:36]=[C:35]([CH2:2][CH2:1][CH:3]2[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]2)[CH:34]=[CH:33][C:25]=1[C:26]([OH:28])=[O:27])(=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 10796Cesium carbonateHCID 12757VinylcyclohexaneHCID 67343005Tert-butyl 2-(benzamido)-4-bromobenzoate

Product 1

HCID 57879584HCID 57879584, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

0.074 mL of vinylcyclohexane, 0.17 g cesium carbonate, 26 mg of tetrabutylammonium bromide and 42 mg of polymer supported di(acetato)dicyclohexylphosphino palladium(II) were added to 2.0 mL of toluene solution containing 0.10 g of tert-butyl 2-(benzamido)-4-bromobenzoate 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 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. 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. 10 mL of trifluoroacetic acid was added to the obtained residue and stirred at room temperature for 1 hour, and the solvent was evaporated under reduced pressure. The obtained residue was purified with reversed-phase silica gel column chromatography [eluent; 60-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to obtain 4.8 mg of 2-(benzamido)-4-(2-cyclohexylethyl)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 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. temperatureAfter the 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-92f2dff6779e42a09f566d08b77c4777
Source dataset
uspto-grants-2011_08
Patent number
US07999132B2

Reaction notes

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