Diethyl Malonate → diethyl 2-[(4-nitrophenyl)methyl]propanedioate

HRID 1861686Notes

Reaction equation

HRID 1861686 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[N+:14]([C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Br)=[CH:19][CH:18]=1)([O-:16])=[O:15]>C1COCC1>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([CH2:21][C:20]1[CH:23]=[CH:24][C:17]([N+:14]([O-:16])=[O:15])=[CH:18][CH:19]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 660114-Nitrobenzyl bromide

Product 1

HCID 348576diethyl 2-[(4-nitrophenyl)methyl]propanedioateYield 68.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Diethyl malonate (7.41 g, 46.3 mmol) was added to a slurry of NaH (60% oil dispersion, 2.04 g, 50.9 mmol) in THF (200 ml) and stirred for 15 min, before adding a solution of 4-nitrobenzyl bromide (10.0 g, 46.3 mmol) in THF (100 ml) by cannula. The reaction was stirred for 3 h at room temperature then quenched by the addition of water (100 ml). The aqueous layer was separated and extracted with Et2O (200 ml). The combined organic layers were washed with brine (200 ml), dried (MgSO4) and the solvent evaporated in vacuo to give an off-white solid. Trituration with Et2O/hexane (1:5, 100 ml), removal of the solid by filtration and concentration of the filtrate in vacuo gave an oil which was purified by chromatography (SiO2;EtOAc/hexane 1:3) to give the title compound as an oil (9.4 g), containing about 20% diethyl malonate. δH (CDCl3) 8.15 (2H, d, J 8.8 Hz, Ar—H), 7.39 (2H, d, J 8.7 Hz, Ar—H), 4.25-4.11 (4H, m, CH2CH3), 3.67 (1H, t, J 7.8 Hz, CHCH2Ar), 3.32 (2H, d, J 7.8 Hz, CHCH2Ar) and 1.23 (6H, t, J 7.2 Hz, CH2CH3).

Workup

  1. stirringThe reaction was stirred for 3 h at room temperature
  2. customthen quenched by the addition of water (100 ml)
  3. customThe aqueous layer was separated
  4. extractionextracted with Et2O (200 ml)
  5. washThe combined organic layers were washed with brine (200 ml)
  6. dry with materialdried (MgSO4)
  7. customthe solvent evaporated in vacuo
  8. customto give an off-white solid
  9. customTrituration with Et2O/hexane (1:5, 100 ml), removal of the solid
  10. filtrationby filtration and concentration of the filtrate in vacuo
  11. customgave an oil which
  12. customwas purified by chromatography (SiO2;EtOAc/hexane 1:3)

Sources & evidence

ORD record
ord-780b654910d943788ec732eabf1e2386
Source dataset
uspto-grants-2003_03
Patent number
US06534513B1

Reaction notes

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