Diethyl Malonate → Diethyl 2-(3-nitropyridin-4-yl)malonate

HRID 2213298Notes

Reaction equation

HRID 2213298 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][N:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22]>C1(C)C=CC=CC=1>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22])[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 27357814-Chloro-3-nitropyridine

Product 1

HCID 12244207Diethyl 2-(3-nitropyridin-4-yl)malonateYield 18.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a suspension of 3.05 g of 60% sodium hydride (76.0 mmol) in toluene (50 mL) in a 250 mL RB flask was added 12.2 g of diethyl malonate (76.0 mmol) dropwise. The reaction mixture was stirred for 30 min under nitrogen, and a solution of 10.8 g of 4-chloro-3-nitropyridine (prepared according to the procedure of Houston et al. J. Med. Chem. 1985, 28, 467) in toluene (50 mL) was added dropwise and the resulting mixture refluxed for 4 hours. The reaction mixture was concentrate, and the residue was partitioned between 100 mL each of dilute hydrochloric acid and diethyl ether. The aqueous phase was extracted twice with 100 mL of ether, and the combined ether phases were dried over magnesium sulfate and concentrated to give a dark oil. This was chromatographed on silica gel eluting with a hexane-30% hexane/EtOAc gradient to give 3.5 g of the title compound as a colorless oil which crystallized on standing. 1H NMR (DMSO-d6): δ 1.15 (t, J=7.1 Hz, 6H), 4.16 (q, J=7.1 Hz, 4H), 5.55 (s, 1H), 7.59 (d, J=5.1 Hz, 1H), 8.89 (d, J=5.1 Hz, 1H), 9.24 (s, 1H); C12H14N2O6: APES-MS m/z 281 (M−H).

Workup

  1. temperaturethe resulting mixture refluxed for 4 hours
  2. concentrationThe reaction mixture was concentrate
  3. customthe residue was partitioned between 100 mL each of dilute hydrochloric acid and diethyl ether
  4. extractionThe aqueous phase was extracted twice with 100 mL of ether
  5. dry with materialthe combined ether phases were dried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give a dark oil
  8. customThis was chromatographed on silica gel eluting with a hexane-30% hexane/EtOAc gradient

Sources & evidence

ORD record
ord-90dea57c92dc4321a1864f991863866f
Source dataset
uspto-grants-2006_09
Patent number
US07105529B2

Reaction notes

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