Methyl iodide → HCID 57544371, compound

HRID 537966Notes

Reaction equation

HRID 537966 reaction equation
[O-][CH2:2]C.[Na+].[F:5][C:6]([F:23])([F:22])[C:7]1[CH:8]=[C:9]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[C:10]([CH2:12][C:13]#[N:14])=[O:11].CI>CCO>[F:5][C:6]([F:22])([F:23])[C:7]1[CH:8]=[C:9]([C:10](=[O:11])[CH:12]([CH3:2])[C:13]#[N:14])[CH:15]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:17]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2723922Sodium ethoxideHCID 247268153-[3,5-Bis(trifluoromethyl)phenyl]-3-oxopropanenitrile

Product 1

HCID 57544371HCID 57544371, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of sodium ethoxide (0.127 g, 1.87 mmol) in EtOH (5 mL) was treated with 3,5-bis(trifluoromethyl)benzoyl acetonitrile (0.500 g, 1.78 mmol) portionwise over 5 min. The reaction was heated at reflux for 30 min before the addition of methyl iodide (0.41 mL, 6.6 mmol). Heating at reflux was continued for a further 2 h before the reaction mixture was allowed to cool and concentrated in vacuo. The residue was partitioned between H2O (10 mL) and EtOAC (20 mL) and the aqueous phase was separated and re-extracted with EtOAC (2×20 mL). The combined organic extracts were washed with brine (25 mL), dried (MgSO4), filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0-20% EtOAc in hexanes gradient) to afford 3-[3,5-bis(trifluoromethyl)phenyl]-2-methyl-3-oxopropanenitrile. 1H NMR (500 MHz, CDCl3) δ 8.21 (s, 2H), 8.10 (s, 1H), 4.42 (q, J=7.1 Hz, 1H), 1.71 (d, J=7.1 Hz, 6H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureHeating
  3. temperatureat reflux
  4. temperatureto cool
  5. concentrationconcentrated in vacuo
  6. customThe residue was partitioned between H2O (10 mL) and EtOAC (20 mL)
  7. customthe aqueous phase was separated
  8. extractionre-extracted with EtOAC (2×20 mL)
  9. washThe combined organic extracts were washed with brine (25 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified by flash chromatography on silica gel (0-20% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-7f589b786d3b4f268f241abe399fcfee
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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