Citric Acid → HCID 66990470, compound

HRID 454679Notes

Reaction equation

HRID 454679 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:13]([O:20][C:21]1[CH:48]=[CH:47][C:46](Br)=[CH:45][C:22]=1[C:23]([NH:25][C:26]1[CH:38]=[C:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:36]=[CH:35][C:27]=1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:24])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>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.C1(C)C=CC=CC=1>[C:31]([O:30][C:28](=[O:29])[C:27]1[CH:35]=[CH:36][C:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:38][C:26]=1[NH:25][C:23](=[O:24])[C:22]1[CH:45]=[C:46]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[CH:47]=[CH:48][C:21]=1[O:20][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)([CH3:34])([CH3:32])[CH3:33]

Participants

10

Reactant 4

HCID 311Citric AcidHCID 8083Morpholine2×HCID 10796Cesium carbonate2×HCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

Product 1

HCID 66990470HCID 66990470, compound

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Morpholine (0.014 mL), cesium carbonate (0.070 g), tris(dibenzylideneacetone)dipalladium(0) (1.0 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (2.6 mg), and palladium(II) acetate (0.5 mg) were added to a toluene (0.90 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.060 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours and 30 minutes. The reaction mixture was cooled to room temperature, and then morpholine (4.7 μL), cesium carbonate (0.035 g), tris(dibenzylideneacetone)dipalladium(0) (1.0 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (2.6 mg), and palladium(II) acetate (0.5 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 2 hours and 30 minutes. The reaction mixture was cooled to room temperature, and a 10% aqueous solution of citric acid 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: 100-60% hexane/ethyl acetate] to obtain 0.060 g of tert-butyl-2-(2-(benzyloxy)-5-(morpholin-4-yl)benzamido)-4-phenylbenzoate as a light yellow solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 2 hours and 30 minutes
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 2 hours and 30 minutes
  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: 100-60% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-423d05dc600c434f8b296e7fac17b120
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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