Diethyl Malonate → 5-Bromo-2-methyl-3-nitropyridine

HRID 734983Notes

Reaction equation

HRID 734983 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([N+:11]([O-:13])=[O:12])[C:7](Cl)=[N:8][CH:9]=1.[C:14](OCC)(=O)CC(OCC)=O>C1COCC1>[Br:3][C:4]1[CH:5]=[C:6]([N+:11]([O-:13])=[O:12])[C:7]([CH3:14])=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydride2×HCID 70194125-Bromo-2-chloro-3-nitropyridine

Product 1

HCID 250672665-Bromo-2-methyl-3-nitropyridineYield 63.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (1.31 g, 54.8 mmol, 2.19 g of 60% in mineral oil) was suspended in dry THF (70 mL) and to this suspension was added 5-bromo-2-chloro-3-nitropyridine as a solid. An ambient water bath was placed under the reaction and a solution of diethyl malonate in dry THF (15 mL) was added carefully via addition funnel. Observed a vigorous evolution of gas. After 2 hours additional sodium hydride (0.202 g, 8.42 mmol, 0.337 g of 60% in mineral oil) was added and the reaction was stirred for 1.5 hours. The reaction was concentrated in vacuo, diluted with 6N HCl (100 ml), and refluxed overnight. The reaction was concentrated in vacuo and diluted with saturated sodium carbonate to pH 9. The basic aqueous mixture was diluted with dichloromethane and filtered through filter paper to remove an insoluble green solid. The filtrate was transferred to a separatory funnel and the layers were separated. The dichloromethane was washed with saturated sodium chloride (aq), dried over sodium sulfate, filtered and concentrated to give the title compound (5.79 g, 63.3%) as an orange oil. MS(ES)+ m/e 217 [M+H].

Workup

  1. customAn ambient water bath was placed under the reaction
  2. concentrationThe reaction was concentrated in vacuo
  3. additiondiluted with 6N HCl (100 ml)
  4. temperaturerefluxed overnight
  5. concentrationThe reaction was concentrated in vacuo
  6. additiondiluted with saturated sodium carbonate to pH 9
  7. additionThe basic aqueous mixture was diluted with dichloromethane
  8. filtrationfiltered
  9. filtrationthrough filter paper
  10. customto remove an insoluble green solid
  11. customThe filtrate was transferred to a separatory funnel
  12. customthe layers were separated
  13. washThe dichloromethane was washed with saturated sodium chloride (aq)
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-0b59c75736af4a649d91c18a80373a39
Source dataset
uspto-grants-2009_09
Patent number
US07592342B2

Reaction notes

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