Dimethyl malonate → 1,3-Dimethyl 2-(4-bromo-2-nitrophenyl)propanedioate

HRID 2096954Notes

Reaction equation

HRID 2096954 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].[Br:12][C:13]1[CH:18]=[CH:17][C:16](F)=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=1>CN(C=O)C>[Br:12][C:13]1[CH:18]=[CH:17][C:16]([CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=1

Participants

5

Reactant 3

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 27363284-Bromo-1-fluoro-2-nitrobenzene

Product 1

HCID 157405961,3-Dimethyl 2-(4-bromo-2-nitrophenyl)propanedioateYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Dimethyl malonate (40.34 g, 0.305 mol) in N,N′-dimethylformamide (45 mL) was added dropwise to a stirred suspension of sodium hydride (60% dispersion in mineral oil, 16.2 g, 405 mmol) in N,N′-dimethylformamide (500 mL) at 10° C. The mixture was stirred for 1 hour at room temperature then 4-bromo-1-fluoro-2-nitrobenzene (44.38 g, 202 mmol) in N,N′-dimethylformamide (45 mL) was added dropwise to the reaction mixture. The mixture was stirred 75 minutes at room temperature and then was warmed to 65° C. After 1 hour, the solvent was removed under reduced pressure, the residue was taken up in a mixture of ethyl acetate and water and 2M aqueous hydrochloric acid was added until the mixture became pale yellow in colour. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated. The crude product was recrystallized from diisopropyl ether to give the title compound (55.0 g, 83%) as a pale yellow solid.

Workup

  1. stirringThe mixture was stirred 75 minutes at room temperature
  2. temperaturewas warmed to 65° C
  3. waitAfter 1 hour
  4. customthe solvent was removed under reduced pressure
  5. additionthe residue was taken up in a mixture of ethyl acetate and water and 2M aqueous hydrochloric acid
  6. additionwas added until the mixture
  7. customThe organic layer was separated
  8. washwashed with water, brine
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customThe crude product was recrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-d51ee943227847d2ba9eb2049762887e
Source dataset
uspto-grants-2013_05
Patent number
US08450341B2

Reaction notes

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