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

HRID 1682975Notes

Reaction equation

HRID 1682975 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].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>C1COCC1>[CH2:29]([O:28][C:26](=[O:27])[CH2:25][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)[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH3:30]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 667273,4-DimethoxybenzeneacetonitrileHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

Combined 3,4-dimethoxy-phenyl-acetonitrile (20.0 g, 113 mmol) and THF (100 mL). Cooled in a dry-ice/acetone bath. Added dropwise, sodium bis(trimethylsilyl)amide (226 mL, 1.0M in THF, 226 mmol, 2 eq.). After the addition was complete, allowed to warm to 10 ° C. Cooled in a dry-ice/acetone bath. Added dropwise, ethyl bromoacetate (37.7 g, 226 mmol). After the addition was complete, the reaction mixture was allowed to warm to ambient temperature and maintained overnight. Filtered the reaction mixture and concentrated in vacuo to obtain a residue. The residue was partitioned between diethyl ether (600 mL) and water (200 mL). The organic layer was extracted with water (200 mL), saturated NH4Cl (2×100 mL), dried over MgSO4, filtered, and concentrated in vacuo to obtain a residue. Chromatographed on silica gel eluting with ethyl acetate/hexane (1:2) to obtain the title compound: Rf =0.42 (silica gel, 1:2 ethyl acetate/hexane).

Workup

  1. temperatureCooled in a dry-ice/acetone bath
  2. additionAdded dropwise
  3. additionAfter the addition
  4. temperatureCooled in a dry-ice/acetone bath
  5. additionAdded dropwise
  6. additionAfter the addition
  7. temperatureto warm to ambient temperature
  8. temperaturemaintained overnight
  9. filtrationFiltered the reaction mixture
  10. concentrationconcentrated in vacuo
  11. customto obtain a residue
  12. customThe residue was partitioned between diethyl ether (600 mL) and water (200 mL)
  13. extractionThe organic layer was extracted with water (200 mL), saturated NH4Cl (2×100 mL)
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customto obtain a residue
  18. customChromatographed on silica gel eluting with ethyl acetate/hexane (1:2)

Sources & evidence

ORD record
ord-dc25476a864d446bb5e7d45b5ac38e04
Source dataset
uspto-grants-1997_06
Patent number
US05635510

Reaction notes

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