Ethanol → Benzoic acid, 4-[(3-amino-2-pyridinyl)amino]-, ethyl ester

HRID 2411198Notes

Reaction equation

HRID 2411198 reaction equation
C(O)C.[Cl-].[NH4+].[N+:6]([C:9]1[C:10]([NH:15][C:16]2[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)([O-])=O>[Fe].O>[NH2:6][C:9]1[C:10]([NH:15][C:16]2[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=2)=[N:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 3097921Ethyl 4-[(3-nitropyridin-2-yl)amino]benzoate

Product 1

HCID 51370225Benzoic acid, 4-[(3-amino-2-pyridinyl)amino]-, ethyl esterYield 91.8%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

To phenol (22.92 g) were added 2-chloro-3-nitropyridine (13.22 g) and potassium iodide (0.42 g), and the mixture was stirred at 100° C. for 10 min. Ethyl 4-aminobenzoate (13.2 g) were added, and the mixture was stirred at 100° C.-150° C. for 6 hr. The reaction mixture was poured into ice water, and 4N aqueous sodium hydroxide solution (63 mL) and ethyl acetate (100 mL) were added. The precipitated solid was collected by filtration, and recrystallized from ethanol to give ethyl 4-(3-nitropyridin-2-ylamino)benzoate (15.48 g). Then, to a solution of ethanol (186 mL) and water (46 mL) were added ammonium chloride (1.12 g) and iron (8.1 g), the mixture was stirred at 60° C.-70° C., and the obtained ethyl 4-(3-nitropyridin-2-ylamino)benzoate (10.67 g) was added. After completion of the reaction, the insoluble material was collected by filtration, and the filtrate was concentrated. To the residue was added aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate, and the solvent was evaporated to give ethyl 4-(3-aminopyridin-2-ylamino)benzoate (8.77 g). To the obtained ethyl 4-(3-aminopyridin-2-ylamino)benzoate (8.77 g) was added triethyl orthoformate (87 mL), and the mixture was stirred with heating under reflux for 4 hr. The solvent was evaporated from the reaction mixture, and toluene (35 mL) and a small amount of p-toluenesulfonic acid hydrate were added to the residue, and the mixture was stirred with heating under reflux for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The solvent was evaporated from the organic layer, and to the residue were added ethylether and hexane, and the precipitated solid was collected by filtration to give the title compound (7.926 g).

Workup

  1. customAfter completion of the reaction
  2. filtrationthe insoluble material was collected by filtration
  3. concentrationthe filtrate was concentrated
  4. additionTo the residue was added aqueous sodium hydrogen carbonate solution
  5. extractionthe mixture was extracted with ethyl acetate
  6. customthe solvent was evaporated

Sources & evidence

ORD record
ord-daca55bfe7fd453cb441360c8b9efff2
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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