Citric Acid → Methyl 4-(2-(tert-butoxycarbonylamino)phenyl)-2-nitrobenzoate

HRID 454515Notes

Reaction equation

HRID 454515 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])O1.Cl[C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[C:33]([N+:41]([O-:43])=[O:42])[CH:32]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OCC)(=O)C.COCCOC.O>[C:24]([O:23][C:22]([NH:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[C:33]([N+:41]([O-:43])=[O:42])[CH:32]=1)=[O:28])([CH3:25])([CH3:26])[CH3:27]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 10340Sodium CarbonateHCID 39135Methyl 4-chloro-2-nitrobenzoateHCID 2773231tert-Butyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate

Product 1

HCID 66989922Methyl 4-(2-(tert-butoxycarbonylamino)phenyl)-2-nitrobenzoateYield 96.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Water (3.0 mL), sodium carbonate (1.1 g), tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (1.5 g), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)palladium(II) dichloride (30 mg) were added to an ethylene glycol dimethyl ether (10 mL) solution of methyl 4-chloro-2-nitrobenzoate (0.90 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 ethyl acetate and a 10% aqueous solution of citric acid were added thereto. 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 [eluent: 95-85% hexane/ethyl acetate] to obtain 1.5 g of methyl 4-(2-(tert-butoxycarbonylamino)phenyl)-2-nitrobenzoate as a light yellow solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour and 30 minutes
  3. customThe organic layer was separated
  4. washwashed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography [eluent: 95-85% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-4e716474637f46d294b5914c16b72e08
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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