Diethyl Malonate → Diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate

HRID 880923Notes

Reaction equation

HRID 880923 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].[Br:14][C:15]1[CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[C:18](Cl)=[N:19][CH:20]=1>CN(C)C=O>[Br:14][C:15]1[CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[C:18]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])=[N:19][CH:20]=1

Participants

5

Reactant 3

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

Product 1

HCID 57516275Diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonateYield 69.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (5.08 g, 127 mmol) in N,N-dimethylformamide (75 mL) was added diethyl malonate (19.26 mL, 127 mmol) at 0° C. The solution was then stirred at ambient temperature for 30 minutes and a solution of 5-bromo-2-chloro-3-nitropyridine (30 g, 127 mmol) in N,N-dimethylformamide (75 mL) was added dropwise. The dark brown mixture was then stirred at 100° C. for 2 hours before being cooled to ambient temperature and quenched with a saturated solution of ammonium chloride (500 mL) at 0° C. The mixture was extracted with ethyl acetate (3×500 mL) and the combined organics were dried over magnesium sulfate and filtered. The solvent was removed in vacuo to give a dark brown oil which was purified by flash column chromatography (10% ethyl acetate/hexane) to afford diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate as a brown solid (31.8 g, 69%). 1HNMR (400 MHz, CDCl3, δ): 8.86 (s, 1H), 8.61 (s, 1H), 5.44 (s, 1H), 4.29 (q, 4H), 1.27 (t, 6H).

Workup

  1. stirringThe dark brown mixture was then stirred at 100° C. for 2 hours
  2. temperaturebefore being cooled to ambient temperature
  3. customquenched with a saturated solution of ammonium chloride (500 mL) at 0° C
  4. extractionThe mixture was extracted with ethyl acetate (3×500 mL)
  5. dry with materialthe combined organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed in vacuo
  8. customto give a dark brown oil which
  9. customwas purified by flash column chromatography (10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9a013eb0ca5f467693f981ddad809312
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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