Toluene → HCID 66990288, compound

HRID 454616Notes

Reaction equation

HRID 454616 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1.[CH2:24]([O:31][C:32]1[CH:59]=[CH:58][C:57](Br)=[CH:56][C:33]=1[C:34]([NH:36][C:37]1[CH:49]=[C:48]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:47]=[CH:46][C:38]=1[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[O:35])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=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(OCC)(=O)C.O>[CH2:24]([O:31][C:32]1[CH:59]=[CH:58][C:57]([N:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)=[CH:56][C:33]=1[C:34]([NH:36][C:37]1[CH:49]=[C:48]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:47]=[CH:46][C:38]=1[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[O:35])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

10

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

Product 1

HCID 66990288HCID 66990288, compound

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,4-Dioxa-8-azaspiro[4,5]decane (0.12 mL), cesium carbonate (0.35 g), tris(dibenzylideneacetone)dipalladium(0) (3.3 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (8.5 mg), and palladium(II) acetate (1.6 mg) were added to a toluene (3.0 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.20 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then tris(dibenzylideneacetone)dipalladium(0) (3.3 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (8.5 mg), and palladium(II) acetate (1.6 mg) were added to the reaction mixture, followed by heating to reflux under a nitrogen atmosphere for 5 hours. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added thereto. The insoluble substance was removed by filtration. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium 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: 90-65% hexane/ethyl acetate] to obtain 0.18 g of tert-butyl 2-(2-(benzyloxy)-5-(1,4-dioxa-8-azaspiro[4,5]decan-8-yl)benzamido)-4-phenylbenzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 2 hours
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 5 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. washwashed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 90-65% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-5bf30bc6728a4f0e8321319c63b477be
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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