Dimethyl malonate → 2-(3-Bromo-5-chloro-phenyl)-malonic acid dimethyl ester

HRID 563678Notes

Reaction equation

HRID 563678 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Br:9])[CH:3]=1.[C:10]([O:17][CH3:18])(=[O:16])[CH2:11][C:12]([O:14][CH3:15])=[O:13].[H-].[Na+].[NH4+].[OH-]>O1CCOCC1.[Cu]Br.C(Cl)Cl>[CH3:15][O:14][C:12](=[O:13])[CH:11]([C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Br:9])[CH:3]=1)[C:10]([O:17][CH3:18])=[O:16]

Participants

8

Reactant 4

HCID 7943Dimethyl malonateHCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 846761,3-Dibromo-5-chlorobenzene

Product 1

HCID 574588062-(3-Bromo-5-chloro-phenyl)-malonic acid dimethyl ester

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

1,3-Dibromo-5-chlorobenzene (25 g, 93 mmol), dimethyl malonate (23.4 mL, 204 mmol), and copper(I) bromide (29.2 g, 204 mmol) were combined in 1,4-dioxane (300 mL) and cooled to 0° C. Sodium hydride (60% in mineral oil; 8.2 g, 204 mmol) was added slowly, and the reaction was stirred at room temperature for 20 minutes, and then stirred at 105° C. for 4 hours. After cooling to room temperature, the mixture was worked-up with CH2Cl2 and aqueous NH4OH. The organic layer was concentrated, and the residue was purified by silica gel chromatography (0-20% EtOAc in hexanes) to give the title compound.

Workup

  1. stirringstirred at 105° C. for 4 hours
  2. temperatureAfter cooling to room temperature
  3. concentrationThe organic layer was concentrated
  4. customthe residue was purified by silica gel chromatography (0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-78f437b81da9473d909fcf55740c3f88
Source dataset
uspto-grants-2011_11
Patent number
US08067445B2

Reaction notes

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