Citric Acid → HCID 66990791, compound

HRID 454507Notes

Reaction equation

HRID 454507 reaction equation
[C:1]1(OB=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:16]([O:23][C:24]1[CH:41]=[CH:40][C:39]([N:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)=[CH:38][C:25]=1[C:26]([NH:28][C:29]1[CH:34]=[C:33](Cl)[CH:32]=[CH:31][C:30]=1[C:36]#[N:37])=[O:27])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)(Cl)Cl.COCCOC.O>[CH2:16]([O:23][C:24]1[CH:41]=[CH:40][C:39]([N:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)=[CH:38][C:25]=1[C:26]([NH:28][C:29]1[CH:34]=[C:33]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:32]=[CH:31][C:30]=1[C:36]#[N:37])=[O:27])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 10340Sodium Carbonate2×HCID 14438906HCID 14438906, compound2×HCID 66989829HCID 66989829, compound

Product 1

HCID 66990791HCID 66990791, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Water (0.74 mL), phenylboranic acid (0.12 g), sodium carbonate (0.21 g), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)palladium(II) dichloride (3.0 mg) were added to an ethylene glycol dimethyl ether (3.0 mL) suspension of the obtained 2-(benzyloxy)-N-(5-chloro-2-cyanophenyl)-5-(piperidin-1-yl)benzamide, followed by heating to reflux under a nitrogen atmosphere for 1 hour. After cooling the reaction mixture to room temperature, phenylboranic acid (0.12 g), sodium carbonate (0.21 g), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)palladium(II) dichloride (3.0 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 40 minutes. The reaction mixture was cooled to room temperature, and then chloroform and a 10% aqueous solution of citric acid were added thereto. The organic layer was separated and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 90-50% hexane/ethyl acetate] to obtain 0.32 g of 2-(benzyloxy)-N-(4-cyanobiphenyl-3-yl)-5-(piperidin-1-yl)benzamide as a yellow solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 40 minutes
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography [eluent: 90-50% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-6728fa4c038744cfb83e74bf78c67344
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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