Acetonitrile → 4-[4-Methoxy-3-(2-methoxyethoxy)phenyl]-3-oxo-butyronitrile

HRID 506155Notes

Reaction equation

HRID 506155 reaction equation
C([Li])CCC.[CH3:6][C:7]#[N:8].C[O:10][C:11](=O)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH2:22][CH2:23][O:24][CH3:25])[CH:14]=1.[NH4+].[Cl-]>C1COCC1.O>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][C:11](=[O:10])[CH2:6][C:7]#[N:8])=[CH:14][C:15]=1[O:21][CH2:22][CH2:23][O:24][CH3:25]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 25517Ammonium ChlorideHCID 684676464-Methoxy-3-(2-methoxyethoxy)phenylacetic acid methyl esterHCID 178418339Butyllithium

Product 1

HCID 684663014-[4-Methoxy-3-(2-methoxyethoxy)phenyl]-3-oxo-butyronitrileYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a 250 mL three-necked round-bottomed flask was added 10 mL of anhydrous THF and cooled to −78° C. n-Butyl lithium (2.5 M in hexane, 8.06 mL, 12.9 mmol) was added and the mixture was stirred for 5 min. Anhydrous CH3CN (0.696 mL, 13.3 mmol) in 5 mL of anhydrous THF was added dropwise at −78° C. After 1 h of stirring, 4-methoxy-3-(2-methoxyethoxy)phenylacetic acid methyl ester (1.10 g, 4.3 mmol) in 10 mL of anhydrous THF was added dropwise to the resulting white colloidal mixture. The reaction mixture was stirred for an additional 2 h, followed by the addition of saturated NH4Cl solution at −78° C. The solution was warmed to r.t., diluted with 100 mL water and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with gradient 30-60% EtOAc in hexanes to yield 769 mg (68% yield) of 4-[4-methoxy-3-(2-methoxyethoxy)phenyl]-3-oxo-butyronitrile as a colorless oil.

Workup

  1. additionwas added
  2. stirringAfter 1 h of stirring
  3. stirringThe reaction mixture was stirred for an additional 2 h
  4. extractionextracted with EtOAc (3×100 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried with anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel eluting with gradient 30-60% EtOAc in hexanes

Sources & evidence

ORD record
ord-ace19b53401d43e2a09d8cc5e9717199
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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