Benzene, 1-bromo-2-(trifluoromethyl)- → HCID 68962012, compound

HRID 2191736Notes

Reaction equation

HRID 2191736 reaction equation
[NH2:1][C:2]1[CH:14]=[C:13]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:12]=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH2:15]([C:13]1[CH:12]=[CH:11][C:3]([C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])=[C:2]([NH:1][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])[CH:14]=1)[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 58508624Tert-butyl 2-amino-4-phenethylbenzoate

Product 1

HCID 68962012HCID 68962012, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To toluene 3.0 mL solution of tert-butyl 2-amino-4-phenethylbenzoate 0.10 g were added 2-bromobenzotrifluoride 0.11 mL, cesium carbonate 0.22 g, tris(dibenzylideneacetone)dipalladium(0) 3.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 8.0 mg at room temperature, and it was stirred at 110° C. for 24 hours. After the reaction mixture was cooled to room temperature, palladium acetate 1.5 mg, tris(dibenzylideneacetone)dipalladium(0) 3.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 8.0 mg were added to it, and it was stirred at 110° C. for 20 hours. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008, eluent; hexane:ethyl acetate=4:1] to give tert-butyl 4-phenethyl-2-(2-(trifluoromethyl)anilino)benzoate.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringwas stirred at 110° C. for 20 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. filtrationinsoluble matter was filtrated
  5. additionethyl acetate and 10% citric acid aqueous solution were added to it
  6. customThe organic layer was separated
  7. customcollected
  8. dry with materialdried over anhydrous magnesium sulfate
  9. washafter washing with saturated sodium chloride aqueous solution
  10. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-ea9127e9b05d46e0b6144c9f2ef07756
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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