Sodium hydride → Tert-butyl ethyl 5-benzyloxy-3-fluoro-4-nitrophenylmalonate

HRID 1372651Notes

Reaction equation

HRID 1372651 reaction equation
[C:1]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[CH2:16]([O:23][C:24]1[CH:29]=[C:28](F)[CH:27]=[C:26]([F:31])[C:25]=1[N+:32]([O-:34])=[O:33])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C>[CH2:16]([O:23][C:24]1[C:25]([N+:32]([O-:34])=[O:33])=[C:26]([F:31])[CH:27]=[C:28]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])[CH:29]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 96345tert-Butyl ethyl malonateHCID 178593022-Benzyloxy-4,6-difluoronitrobenzene

Product 1

HCID 67406365Tert-butyl ethyl 5-benzyloxy-3-fluoro-4-nitrophenylmalonateYield 19.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of tert-butyl ethyl malonate (10.0 g, 51.0 mmol) in DMF (200 ml) was added sodium hydride (60% in oil, 2.04 g, 51.0 mmol) at 0° C. under stirring. The reaction mixture was stirred at the same temperature for 30 minutes. A solution of 2-benzyloxy-4,6-difluoronitrobenzene (9.02 g, 34.0 mmol) in DMF (60 ml) was added dropwise to the reaction mixture at 0° C. The reaction mixture was then stirred at 80° C. for 18 hours. After cooling to room temperature, the reaction mixture was poured in ice-1N HCl to neutralize therewith, followed by extraction with ether. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, then distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from with ethyl acetate/hexane (1/5) eluate fractions, tert-butyl ethyl 5-benzyloxy-3-fluoro-4-nitrophenylmalonate (2.91 g, 17%) was obtained as a yellow oil.

Workup

  1. stirringThe reaction mixture was stirred at the same temperature for 30 minutes
  2. stirringThe reaction mixture was then stirred at 80° C. for 18 hours
  3. extractionfollowed by extraction with ether
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customThe residue was purified by chromatography on a silica gel column, whereby from with ethyl acetate/hexane (1/5) eluate fractions

Sources & evidence

ORD record
ord-a6aab00029764b4592a7f7c11df056e7
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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