Cesium carbonate → Tert-butyl 2-(4-morpholinoanilino)-4-phenethylbenzoate

HRID 2191751Notes

Reaction equation

HRID 2191751 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][C:27]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[CH:26][CH:25]=1.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>[O:33]1[CH2:34][CH2:35][N:30]([C:27]2[CH:28]=[CH:29][C:24]([NH:1][C:2]3[CH:14]=[C:13]([CH2:15][CH2:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH:12]=[CH:11][C:3]=3[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])=[CH:25][CH:26]=2)[CH2:31][CH2:32]1

Participants

8

Reactant 4

HCID 10796Cesium carbonate2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl3×HCID 116228514-(4-Bromophenyl)morpholine2×HCID 58508624Tert-butyl 2-amino-4-phenethylbenzoate

Product 1

HCID 68957258Tert-butyl 2-(4-morpholinoanilino)-4-phenethylbenzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst3×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 4-(4-bromophenyl)morpholine 0.21 g, cesium carbonate 0.23 g, tris(dibenzylideneacetone)dipalladium(0) 3.2 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 8.3 mg at room temperature, and it was stirred at 110° C. for 6 hours. After the reaction mixture was cooled to room temperature, palladium acetate 1.6 mg, tris(dibenzylideneacetone)dipalladium(0) 3.2 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 8.3 mg were added, and it was stirred at 110° C. for 12 hours. After the reaction mixture was cooled to room temperature, 4-(4-bromophenyl)morpholine 0.21 g, cesium carbonate 0.23 g, palladium acetate 1.6 mg, tris(dibenzylideneacetone)dipalladium(0) 3.2 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 8.3 mg were added, and it was stirred at 110° C. for 4 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 2-(4-morpholinoanilino)-4-phenethylbenzoate.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringit was stirred at 110° C. for 12 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. stirringit was stirred at 110° C. for 4 hours
  5. temperatureAfter the reaction mixture was cooled to room temperature
  6. filtrationinsoluble matter was filtrated
  7. additionethyl acetate and 10% citric acid aqueous solution were added to it
  8. customThe organic layer was separated
  9. customcollected
  10. dry with materialdried over anhydrous magnesium sulfate
  11. washafter washing with saturated sodium chloride aqueous solution
  12. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-de50cfe7c8864ba981a8d9c7022bf76c
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

Loading…