Diethyl Malonate → Diethyl 2-(5-nitropyridin-2-yl)malonate

HRID 374418Notes

Reaction equation

HRID 374418 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+].Cl[C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][N:16]=1>O1CCCC1>[N+:21]([C:18]1[CH:19]=[CH:20][C:15]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])=[N:16][CH:17]=1)([O-:23])=[O:22]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 783082-Chloro-5-nitropyridine

Product 1

HCID 2794558Diethyl 2-(5-nitropyridin-2-yl)malonateYield 63.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Diethyl malonate (74 g) was added to a stirred suspension of sodium hydride (60% dispersion in oil; 18 g) in dry tetrahydrofuran under an inert atmosphere. The resulting suspension was stirred at reflux for one hour. The mixture was cooled to 60° C. and a solution of 2-chloro-5-nitropyridine (50 g) in dry tetrahydrofuran was added. The resulting red solution was stirred at reflux for 3 hours then allowed to stand at room temperature overnight. The volume of solvent was reduced by evaporation, water was added to the residue and the mixture was acidified to pH 1 with concentrated hydrochloric acid. The mixture was extracted with ethyl acetate, washed with water, dried (anhydrous magnesium sulphate), filtered and evaporated. The crude product was triturated in a mixture of cyclohexane and diethyl ether to yield diethyl 2-(5-nitropyridin-2-yl)malonate (56.5 g) as a yellow solid, m.p. 91.5°-93.5° C.

Workup

  1. temperatureat reflux for one hour
  2. stirringThe resulting red solution was stirred
  3. temperatureat reflux for 3 hours
  4. customThe volume of solvent was reduced by evaporation, water
  5. additionwas added to the residue
  6. extractionThe mixture was extracted with ethyl acetate
  7. washwashed with water
  8. dry with materialdried (anhydrous magnesium sulphate)
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was triturated in a mixture of cyclohexane and diethyl ether

Sources & evidence

ORD record
ord-083cab1b1ace4f1199defcbca01b8670
Source dataset
uspto-grants-1996_01
Patent number
US05480857

Reaction notes

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