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

HRID 1965052Notes

Reaction equation

HRID 1965052 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+].[Br:14][C:15]1[CH:16]=[C:17]([Cl:22])[C:18](Cl)=[N:19][CH:20]=1>CN(C=O)C>[Br:14][C:15]1[CH:16]=[C:17]([Cl:22])[C:18]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])=[N:19][CH:20]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 127477605-Bromo-2,3-dichloropyridine

Product 1

HCID 67979448Diethyl 2-(5-bromo-3-chloropyridin-2-yl)malonateYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diethyl malonate (0.87 mL, 5.7 mmol) was added dropwise to a suspension of NaH (55% in mineral oil, 0.27 g, 6.2 mmol) in DMF (6 mL) at 0° C. The ice-bath was removed and the mixture was stirred under N2 at r.t. for 20 min. 5-Bromo-2,3-dichloropyridine (1.0 g, 4.4 mmol) was added, and the mixture was stirred at 120° C. overnight. The mixture was allowed to cool and was then partitioned between water containing NaCl and EtOAc. The organic phase was dried (MgSO4) and evaporated to give a crude product which was purified by flash chromatography (25 g SiO2, heptane/EtOAc gradient) affording the title compound (0.8 g, 2 mmol, 52% yield) containing a residue of unreacted malonic ester. MS (ES+) m/z 350 [M+H]+. A part of this material was used as such in the subsequent step.

Workup

  1. customThe ice-bath was removed
  2. stirringthe mixture was stirred at 120° C. overnight
  3. temperatureto cool
  4. customwas then partitioned between water
  5. additioncontaining NaCl and EtOAc
  6. dry with materialThe organic phase was dried (MgSO4)
  7. customevaporated
  8. customto give a crude product which
  9. customwas purified by flash chromatography (25 g SiO2, heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-a4e9ac45b4a74ac19e35f230e0345bb5
Source dataset
uspto-grants-2013_04
Patent number
US08415483B2

Reaction notes

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