Diethyl Malonate → Diethyl (3-nitropyridin-2-yl)propanedioate

HRID 840941Notes

Reaction equation

HRID 840941 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[C:20]([N+:21]([O-:23])=[O:22])=[CH:19][CH:18]=[CH:17][N:16]=1.[Cl-].[NH4+]>CS(C)=O>[N+:21]([C:20]1[C:15]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])=[N:16][CH:17]=[CH:18][CH:19]=1)([O-:23])=[O:22]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 796132-Chloro-3-nitropyridine

Product 1

HCID 13147345Diethyl (3-nitropyridin-2-yl)propanedioateYield 73.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Sodium hydride (60% dispersion in oil, 5.57 g, 0.14 mol) was carefully washed with hexanes under nitrogen before the addition of DMSO (115 mL). Diethyl malonate (22.3 g, 0.14 mol) was added dropwise over 20 min, and the mixture was stirred for an additional 30 min at room temperature. 2-Chloro-3-nitropyridine (10 g, 0.06 mol) was added to the reaction, and the reaction was placed in a pre-heated oil bath set to 100° C. for 15 min. The reaction was cooled to room temperature and poured into aqueous ammonium chloride (saturated solution, 150 mL). The aqueous solution was extracted with EtOAc:hexanes (1:1) four times (200 mL each), and the organic layers were combined. The organics were concentrated to afford a solid that was recrystallized from a minimal amount EtOAc:hexanes (1:1) to provide the title compound (12.5 g, 70% yield). APCI MS m/z 281 (M−H).

Workup

  1. customthe reaction was placed in a pre-heated oil bath
  2. waitset to 100° C. for 15 min
  3. temperatureThe reaction was cooled to room temperature
  4. extractionThe aqueous solution was extracted with EtOAc:hexanes (1:1) four times (200 mL each)
  5. concentrationThe organics were concentrated
  6. customto afford a solid
  7. customthat was recrystallized from a minimal amount EtOAc:hexanes (1:1)

Sources & evidence

ORD record
ord-f1ed892ac42f47baa1fe173634cdb290
Source dataset
uspto-grants-2002_04
Patent number
US06369086B1

Reaction notes

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