Dimethylformamide → Ethyl 2-(4-cyano-3-methoxyphenyl)acetate

HRID 1186982Notes

Reaction equation

HRID 1186982 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9](OS(C(F)(F)F)(=O)=O)=[C:8]([O:20][CH3:21])[CH:7]=1)[CH3:2].[CH3:23][N:24](C)C=O>O.C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:23]#[N:24])=[C:8]([O:20][CH3:21])[CH:7]=1)[CH3:2]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 58820079Ethyl (3-methoxy-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)acetate

Product 1

HCID 66643843Ethyl 2-(4-cyano-3-methoxyphenyl)acetate

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

The crude ethyl(3-methoxy-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)acetate (16.61 g) was subsequently dissolved in anhydrous dimethylformamide (100 mL). Zinc cyanide (3.42 g, 29.1 mmol) was added, and the solution was purged thoroughly with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (5.61 g, 4.85 mmol) was then added and the reaction mixture was heated to 80° C. for 4 h. After allowing the reaction mixture to cool to ambient temperature and diluting with water (200 mL), ethyl acetate (400 mL) was added. The combined layers were filtered to remove any solids, the filtrate transferred to a separatory funnel, and the layers separated. The aqueous layer was re-extracted with ethyl acetate (2×100 mL), the organic portions were combined and dried over magnesium sulfate. The dry organics were then filtered and evaporated to dryness under reduced pressure and excess dimethylformamide was removed by evaporation in vacuo at 65° C. for 1.5 h to yield the crude title compound (20 g). The crude product was purified through silica gel chromatography (ethyl acetate/hexanes, 2:3) to yield ethyl(4-cyano-3-methoxyphenyl)acetate. NMR (500 MHz, DMSO-d6), δ 7.67 (d, J=8.0 Hz, 1H), 7.18 (s, 1H), 7.0 (d, J=8.0 Hz, 1H), 4.10 (q, J=7.1 Hz, 2H), 3.89 (s, 3H), 3.78 (s, 2H), 1.19 (t, J=7.1 Hz, 3H); LC/MS (M+1)+=220.17; tR=1.36 min.

Workup

  1. customthe solution was purged thoroughly with nitrogen
  2. temperatureto cool to ambient temperature
  3. additionwas added
  4. filtrationThe combined layers were filtered
  5. customto remove any solids
  6. customthe filtrate transferred to a separatory funnel
  7. customthe layers separated
  8. extractionThe aqueous layer was re-extracted with ethyl acetate (2×100 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationThe dry organics were then filtered
  11. customevaporated to dryness under reduced pressure and excess dimethylformamide
  12. customwas removed by evaporation in vacuo at 65° C. for 1.5 h
  13. customto yield the crude title compound (20 g)
  14. customThe crude product was purified through silica gel chromatography (ethyl acetate/hexanes, 2:3)

Sources & evidence

ORD record
ord-64dab7e3d9994977a8c5ee84a1e6e446
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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