Diethyl Malonate → Diethyl (4-methoxy-2-nitrophenyl)malonate

HRID 1914689Notes

Reaction equation

HRID 1914689 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[N+:23]([O-:25])=[O:24].C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O.[F-].[Cs+]>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])=[C:16]([N+:23]([O-:25])=[O:24])[CH:17]=1

Participants

8

Reactant 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 251404-Chloro-3-nitroanisoleHCID 516892Sodium Bicarbonate

Product 1

HCID 1811374Diethyl (4-methoxy-2-nitrophenyl)malonate

Reagents, catalysts & solvents 3

HCID 25953Cesium fluorideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of sodium hydride (2.81 g; 117.28 mmol; 2.2 eq) in DMF (35 mL) under nitrogen is added slowly at 0° C. over 20 min diethyl malonate (17.89 mL; 117.28 mmol; 2.2 eq) followed by cesium fluoride (404.91 mg; 2.67 mmol; 0.05 eq) and 1-chloro-4-methoxy-2-nitrobenzene (10 g; 53.31 mmol; 1 eq; commercially available from ACROS). The resulting reaction mixture is stirred at room temperature for 45 min then heated at 105° C. overnight. The reaction is quenched by addition of water and DMF is removed under reduced pressure. The residue obtained is taken up in EtOAc then an aqueous solution of NaHCO3 is added. The organic phase is separated and dried over MgSO4. The solvent is removed under reduced pressure to afford 25 g of a brown oil which is purified on silica gel (800 g) using cyclohexane/EtOAc (95/5) as eluent affording 4.7 g (28%) of the title compound as a yellow oil. HPLC (max plot) 89%; Rt 4.25 min. LC/MS: (ES+): 312.1, (ES−): 310.1.

Workup

  1. customThe resulting reaction mixture
  2. temperaturethen heated at 105° C. overnight
  3. customThe reaction is quenched by addition of water and DMF
  4. customis removed under reduced pressure
  5. customThe residue obtained
  6. customThe organic phase is separated
  7. dry with materialdried over MgSO4
  8. customThe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-742be963d2e44e1bbb026866435380b4
Source dataset
uspto-grants-2013_12
Patent number
US08614215B2

Reaction notes

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