Diethyl Malonate → 3-(2-Nitrophenyl)propionic acid

HRID 1822869Notes

Reaction equation

HRID 1822869 reaction equation
[H-].[Na+].[C:3]([O:11]CC)(=[O:10])[CH2:4][C:5](OCC)=O.BrC[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[N+:22]([O-:24])=[O:23]>CN(C=O)C.O>[N+:22]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:5][CH2:4][C:3]([OH:11])=[O:10])([O-:24])=[O:23]

Participants

6

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 77569alpha-Bromo-2-nitrotoluene

Product 1

HCID 748183-(2-Nitrophenyl)propionic acidYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in paraffin oil, 1.0 g, 25 mmol) was added to a solution of diethyl malonate (3.2 g, 20 mmol) in DMF (20 ml) and the mixture was stirred for 3 min. 1-Bromomethyl-2-nitrobenzene (4.3 g, 20 mmol) was then added in portions during 5 min. The reaction mixture was stirred for 3 h, diluted with water, and extracted twice with ethyl acetate. The combined organic phases was washed with water and evaporated. The residue was suspended in acetic acid (40 ml) and 7.5 M HCl (10 ml) was added. The mixture was refluxed for 19 h, cooled and partitioned between diethyl ether and saturated aqueous NaHCO3. The organic phase was washed with saturated aqueous NaHCO3 and then acidified with 2M HCl. The precipitate was collected by filtration and dried to give the title compound (2.22 g, 77%).

Workup

  1. stirringThe reaction mixture was stirred for 3 h
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic phases was washed with water
  4. customevaporated
  5. addition7.5 M HCl (10 ml) was added
  6. temperatureThe mixture was refluxed for 19 h
  7. temperaturecooled
  8. custompartitioned between diethyl ether and saturated aqueous NaHCO3
  9. washThe organic phase was washed with saturated aqueous NaHCO3
  10. filtrationThe precipitate was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-cfbd9d96e89e4e48a3f0a0c898de481e
Source dataset
uspto-grants-2006_05
Patent number
US07037925B2

Reaction notes

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