Diethyl methylmalonate → Diethyl 2-(2-bromo-4-nitrophenyl)-2-methylmalonate

HRID 1805170Notes

Reaction equation

HRID 1805170 reaction equation
[CH3:1][CH:2]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[Br:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1F>CN(C=O)C>[Br:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1[C:2]([CH3:1])([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

5

Reactant 3

HCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 696992-Bromo-1-fluoro-4-nitrobenzene

Product 1

HCID 59206132Diethyl 2-(2-bromo-4-nitrophenyl)-2-methylmalonateYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of diethyl 2-methylpropanedioate (21.8 g, 125.0 mmol) in anhydrous DMF (125 mL) was slowly added NaH (5.2 g, 130 mmol) at 0° C. under an atmosphere of nitrogen. The resulting reaction mixture was allowed to stir for 10 minutes at 0° C., and then at room temperature for 10 minutes. 2-bromo-1-fluoro-4-nitro-benzene (25.0 g, 113.6 mmol) was quickly added and the reaction mixture turned bright red. After stirring for 10 minutes at room temperature, the crude mixture was evaporated to dryness and then partitioned between dichloromethane and brine. The layers were separated and the combined organic layers were dried over anhydrous Na2SO4 and evaporated under vacuum to give the crude product, which was purified by silica gel column chromatography (petroleum ether/EtOAc 10:1) to give diethyl 2-(2-bromo-4-nitrophenyl)-2-methylmalonate (33.0 g, 78%)

Workup

  1. customat 0° C.
  2. customThe resulting reaction mixture
  3. waitat room temperature for 10 minutes
  4. stirringAfter stirring for 10 minutes at room temperature
  5. customthe crude mixture was evaporated to dryness
  6. custompartitioned between dichloromethane and brine
  7. customThe layers were separated
  8. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  9. customevaporated under vacuum
  10. customto give the crude product, which
  11. customwas purified by silica gel column chromatography (petroleum ether/EtOAc 10:1)

Sources & evidence

ORD record
ord-f909592628d9483ca4c288a0c31f6030
Source dataset
uspto-grants-2013_01
Patent number
US08354427B2

Reaction notes

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