Ethyl bromoacetate → 3-Cyano-3-(3,4-dimethoxyphenyl)pentanedioic diethyl ester

HRID 343490Notes

Reaction equation

HRID 343490 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12]#[N:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O1CCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].[C:36]([O:39][CH2:40][CH3:41])(=[O:38])[CH3:37].CCCCCC>>[CH2:34]([O:33][C:31](=[O:32])[CH2:30][C:11]([C:12]#[N:13])([C:5]1[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH2:37][C:36]([O:39][CH2:40][CH3:41])=[O:38])[CH3:35]

Participants

6

Reactant 5

HCID 7748Ethyl bromoacetate2×HCID 8028TetrahydrofuranHCID 667273,4-DimethoxybenzeneacetonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 21226206Ethyl acetate hexane

Product 1

HCID 153920193-Cyano-3-(3,4-dimethoxyphenyl)pentanedioic diethyl ester

Conditions

Temperature
10 °C

Procedure

Combine 3,4-dimethoxyphenylacetonitrile (20 g, 113 mmol) and anhydrous tetrahydrofuran (100 mL). Cool in a dry-ice/acetone bath. Add dropwise a solution of sodium bis(trimethylsilyl)amide (226 mL, 1M in tetrahydrofuran, 226 mmol). When the addition is complete warm the reaction mixture to 10° C. and allow to stir for 15 minutes. Cool in a dry-ice/acetone bath, add dropwise ethyl bromoacetate (37.7 g, 226 mmol). When the addition of ethyl bromoacetate is complete, warm the reaction mixture to ambient temperature. After 18 hours, partition the reaction mixture between diethyl ether and water. Extract the organic layer with water and saturated aqueous solution of ammonium chloride. Separate the organic layer, dry over MgSO4, filter, and concentrate invacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 33% ethyl acetate/hexane. Remove residual solvent invacuo at 82° C. to give the title compound: Rf =0.37 (silica gel, 33% ethyl acetate/hexane). Elemental Analysis calculated for C18H23NO6 : C 61.88; H 6.64; N 4.01; Found: C 61.79; H 6.62; N 3.91.

Workup

  1. temperatureCool in a dry-ice/acetone bath
  2. additionWhen the addition
  3. temperatureCool in a dry-ice/acetone bath
  4. temperaturewarm the reaction mixture to ambient temperature
  5. waitAfter 18 hours
  6. custompartition the reaction mixture between diethyl ether and water
  7. extractionExtract the organic layer with water and saturated aqueous solution of ammonium chloride
  8. customSeparate the organic layer
  9. dry with materialdry over MgSO4
  10. filtrationfilter
  11. concentrationconcentrate invacuo
  12. customto obtain a residue
  13. customRemove residual solvent invacuo at 82° C.

Sources & evidence

ORD record
ord-bb3bb34c87884815a2df3e56313ee0f1
Source dataset
uspto-grants-1999_01
Patent number
US05861417

Reaction notes

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