Ethyl Acetate → Ethyl 2-fluoro-5-nitro-α-oxo-4-pyridinepropanoate

HRID 2358154Notes

Reaction equation

HRID 2358154 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[C:12]([O:17][CH2:18][CH3:19])(=[O:16])[C:13]([O-])=[O:14].N12CCCN=C1CCCCC2.C(OCC)(=O)C>C(O)(=O)C.O>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][C:13](=[O:14])[C:12]([O:17][CH2:18][CH3:19])=[O:16])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27831772-Fluoro-4-methyl-5-nitropyridineHCID 21943339Ethanedioic acid, monoethyl ester

Product 1

HCID 67545975Ethyl 2-fluoro-5-nitro-α-oxo-4-pyridinepropanoateYield 46.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

2 g (12.81 mmol) of 2-fluoro-4-methyl-5-nitropyridine and 9.36 g (32.03 mmol) of ethyl oxalate are placed in a 100 ml three-necked flask equipped with a magnetic stirrer and maintained under a flush of nitrogen. 2.11 ml (14.09 mmol) of 1,8-diazabicyclo-[5.4.0]undec-7-ene are then added to the reaction medium stirred at room temperature. The reaction mixture is then stirred at room temperature for 4 hours. A mixture of ethyl acetate (100 ml), water (40 ml) and acetic acid (2 ml) is then added. The mixture is extracted twice with ethyl acetate. The combined organic phases are washed with 100 ml of water and with 100 ml of saturated aqueous sodium chloride solution, dried over sodium sulfate and then concentrated under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with a mixture of heptane and ethyl acetate. 1.53 g of product are thus isolated, and are used without further purification in the following step.

Workup

  1. customequipped with a magnetic stirrer
  2. temperaturemaintained under
  3. customa flush of nitrogen
  4. stirringThe reaction mixture is then stirred at room temperature for 4 hours
  5. additionis then added
  6. extractionThe mixture is extracted twice with ethyl acetate
  7. washThe combined organic phases are washed with 100 ml of water and with 100 ml of saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by chromatography on a column of silica
  11. washeluting with a mixture of heptane and ethyl acetate

Sources & evidence

ORD record
ord-44a10f4c0b95410dab0de53fe146fcb2
Source dataset
uspto-grants-2010_07
Patent number
US07763636B2

Reaction notes

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