Toluene → Tert-butyl 2-(2-(benzyloxy)-5-(thiomorpholin-4-yl)benzamido)-4-phenylbenzoate

HRID 454600Notes

Reaction equation

HRID 454600 reaction equation
[NH:1]1[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1.[CH2:20]([O:27][C:28]1[CH:55]=[CH:54][C:53](Br)=[CH:52][C:29]=1[C:30]([NH:32][C:33]1[CH:45]=[C:44]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:43]=[CH:42][C:34]=1[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[O:31])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=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>[CH2:20]([O:27][C:28]1[CH:55]=[CH:54][C:53]([N:1]2[CH2:6][CH2:5][S:4][CH2:3][CH2:2]2)=[CH:52][C:29]=1[C:30]([NH:32][C:33]1[CH:45]=[C:44]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:43]=[CH:42][C:34]=1[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[O:31])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

10

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonate2×HCID 67164Thiomorpholine2×HCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

Product 1

HCID 66990549Tert-butyl 2-(2-(benzyloxy)-5-(thiomorpholin-4-yl)benzamido)-4-phenylbenzoate

Reagents, catalysts & solvents 5

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

Procedure

Thiomorpholine (0.14 mL), cesium carbonate (0.58 g), tris(dibenzylideneacetone)dipalladium(0) (8.2 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (21 mg), and palladium(II) acetate (4.0 mg) were added to a toluene (5.0 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.50 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then thiomorpholine (0.045 mL), cesium carbonate (0.15 g), tris(dibenzylideneacetone)dipalladium(0) (8.2 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (21 mg), and palladium(II) acetate (4.0 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 3 hours. The reaction mixture was cooled to room temperature, and then water and ethyl acetate were added thereto. The insoluble substance was removed by filtration. The organic layer was separated, washed with a 10% aqueous solution of citric acid and a saturated aqueous solution of sodium chloride sequentially, 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: 100-80% hexane/ethyl acetate] to obtain 0.36 g of tert-butyl 2-(2-(benzyloxy)-5-(thiomorpholin-4-yl)benzamido)-4-phenylbenzoate as a yellow solid.

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 3 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 10% aqueous solution of citric acid
  9. dry with materiala saturated aqueous solution of sodium chloride sequentially, and dried 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: 100-80% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-e0c0db590f854e099093ba02e779dd42
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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