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

HRID 2414738Notes

Reaction equation

HRID 2414738 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 of 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 of EtOAc:hexanes (1:1)

Sources & evidence

ORD record
ord-da7d1dbc9c024bba8a2c3c3051e4321b
Source dataset
uspto-grants-2004_11
Patent number
US06815439B2

Reaction notes

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