Toluene → Tert-butyl 2-(2-(benzyloxy)-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoate

HRID 454610

Reaction equation

HRID 454610 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1.[CH2:26]([O:33][C:34]1[CH:61]=[CH:60][C:59](Br)=[CH:58][C:35]=1[C:36]([NH:38][C:39]1[CH:51]=[C:50]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH:49]=[CH:48][C:40]=1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[O:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=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.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(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(Cl)(Cl)Cl.O>[CH2:26]([O:33][C:34]1[CH:61]=[CH:60][C:59]([N:2]([CH3:1])[CH2:3][CH2:4][N:5]2[CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)=[CH:58][C:35]=1[C:36]([NH:38][C:39]1[CH:51]=[C:50]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH:49]=[CH:48][C:40]=1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[O:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

10

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, Tribasic2×HCID 14979282Methyl(2-(morpholin-4-yl)ethyl)amine2×HCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

Product 1

HCID 66990678Tert-butyl 2-(2-(benzyloxy)-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoateYield 71.9%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst2×HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

N-Methyl-2-(morpholin-4-yl)ethylamine (0.097 g), tripotassium phosphate (0.17 g), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.4 mg), and palladium(II) acetate (1.2 mg) were added to a toluene (2.3 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.15 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour and 30 minutes. The reaction mixture was cooled to room temperature, and then N-methyl-2-(morpholin-4-yl)ethylamine (0.019 g), tripotassium phosphate (0.029 g), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.4 mg) and palladium(II) acetate (1.2 mg) were added to the reaction mixture, followed by heating to reflux under a nitrogen atmosphere for 6 hours. The reaction mixture was cooled to room temperature, and then water and chloroform were added thereto. The insoluble substance was removed by filtration. The organic layer was separated and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol] to obtain 0.12 g of tert-butyl 2-(2-(benzyloxy)-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour and 30 minutes
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 6 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customThe insoluble substance was removed by filtration
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% chloroform/methanol]

Sources & evidence

ORD record
ord-7c23642f12df40259d96040db23b558e
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Linked notes

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