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

HRID 2387994Notes

Reaction equation

HRID 2387994 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([O-:7])=[O:6].[Br:12][C:13]1[CH:14]=[C:15]([N+:20]([O-:22])=[O:21])[C:16](Cl)=[N:17][CH:18]=1.[CH3:23][C:24](O)=O>CN(C=O)C>[Br:12][C:13]1[CH:14]=[C:15]([N+:20]([O-:22])=[O:21])[C:16]([CH:4]([C:5]([O:7][CH2:23][CH3:24])=[O:6])[C:3]([O:9][CH2:10][CH3:11])=[O:8])=[N:17][CH:18]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 3595298Propanedioic acid, monoethyl esterHCID 70194125-Bromo-2-chloro-3-nitropyridine

Product 1

HCID 57516275Diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonateYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (60% in mineral oil, 27.9 g, 0.69 mol) in DMF (300 mL) at 5-10° C. was slowly added ethyl malonate (125 mL, 0.69 mol) over 30 min. The mixture was allowed to stir for 20 min at rt, during which time the suspension became a solution. A solution of 5-bromo-2-chloro-3-nitropyridine (75 g, 0.32 mol) in DMF (75 mL) was added slowly at 5-10° C. The resulting dark red mixture was allowed to stir at 40° C. for 2 h. The reaction mixture was then poured into 1M AcOH (0.75 L) and extracted with DCM (3×250 mL). The organic solutions were combined, washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give diethyl (5-bromo-3-nitropyridin-2-yl)malonate (260 g, 99%) as a yellow oil.

Workup

  1. customover 30 min
  2. stirringto stir at 40° C. for 2 h
  3. extractionextracted with DCM (3×250 mL)
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ffb28c040936483bb9cb55a822ef7657
Source dataset
uspto-grants-2012_09
Patent number
US08268992B2

Reaction notes

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