Potassium Carbonate → 6-Ethoxycarbonylmethoxy-5-nitro-nicotinic acid methyl ester

HRID 2421879Notes

Reaction equation

HRID 2421879 reaction equation
Cl[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[OH:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CN(C=O)C>[CH2:20]([O:19][C:17](=[O:18])[CH2:16][O:15][C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1)[CH3:21]

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 12184Ethyl Glycolate2×HCID 346961Methyl 6-chloro-5-nitronicotinate

Product 1

HCID 578967336-Ethoxycarbonylmethoxy-5-nitro-nicotinic acid methyl esterYield 61.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 6-chloro-5-nitronicotinate (3 g, 13.85 mmol) in THF (60 mL) and DMF (30.0 mL) was added ethyl 2-hydroxyacetate (1.573 mL, 16.62 mmol) and potassium carbonate (5.74 g, 41.6 mmol). The reaction was stirred at room temperature for 24 hours. TLC analysis of the reaction mixture indicated partial consumption of starting material. Ethyl 2-hydroxyacetate (1 mL, 10.57 mmol) and potassium carbonate (2 g, 14.5 mmol) were added and the reaction was stirred at room temperature for 72 hours. TLC analysis of the reaction mixture indicated nearly complete consumption of starting material. The reaction mixture was partially concentrated under reduced pressure for removal of THF. The resulting red solution was diluted with H2O (200 mL) and 1N HCl was added to adjust the pH to 7. The aqueous layer was extracted with EtOAc (3×200 mL). The combined organics were dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was purified by flash column chromatography using a gradient elution of hexanes with 10-70% EtOAc to provide methyl 6-(2-ethoxy-2-oxoethoxy)-5-nitronicotinate (2.43 g, 8.55 mmol, 61.7% yield) as a white solid.

Workup

  1. customconsumption of starting material
  2. stirringthe reaction was stirred at room temperature for 72 hours
  3. customconsumption of starting material
  4. concentrationThe reaction mixture was partially concentrated under reduced pressure for removal of THF
  5. additionThe resulting red solution was diluted with H2O (200 mL) and 1N HCl
  6. additionwas added
  7. extractionThe aqueous layer was extracted with EtOAc (3×200 mL)
  8. dry with materialThe combined organics were dried over anhydrous Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe resulting solid was purified by flash column chromatography
  11. washa gradient elution of hexanes with 10-70% EtOAc

Sources & evidence

ORD record
ord-46baca93e698459f9d91c22fe05f800a
Source dataset
uspto-grants-2011_06
Patent number
US07960377B2

Reaction notes

Loading…