Potassium Cyanide → 4-Acetyl-6-chloro-3-ethoxy-2-iodobenzonitrile

HRID 511038Notes

Reaction equation

HRID 511038 reaction equation
[Cl:1][C:2]1[C:3](F)=[C:4]([I:14])[C:5]([O:11][CH2:12][CH3:13])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[C-:16]#[N:17].[K+]>CN(C=O)C.O>[C:8]([C:6]1[CH:7]=[C:2]([Cl:1])[C:3]([C:16]#[N:17])=[C:4]([I:14])[C:5]=1[O:11][CH2:12][CH3:13])(=[O:10])[CH3:9]

Participants

5

Reactant 2

HCID 9032Potassium CyanideHCID 866669601-(5-Chloro-2-ethoxy-4-fluoro-3-iodophenyl)ethanone

Product 1

HCID 866669594-Acetyl-6-chloro-3-ethoxy-2-iodobenzonitrileYield 77.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)ethanone (1.0 g, 2.9 mmol, from Example 211, Step 1) and potassium cyanide (0.29 g, 4.4 mmol) in DMF (11 mL) was stirred at 40° C. for 3 hours. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×75 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude orange oil. The crude material was dissolved in 1:1 hexane/dichloromethane and purified by flash column chromatography using EtOAc in hexanes (0%-30% over 30 min) to give the desired product (0.79 g, 77%). LCMS for C11H10ClINO2 (M+H)+: m/z=349.9. Found: 349.9.

Workup

  1. extractionextracted with EtOAc (2×75 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a crude orange oil
  6. dissolutionThe crude material was dissolved in 1:1 hexane/dichloromethane
  7. custompurified by flash column chromatography
  8. customEtOAc in hexanes (0%-30% over 30 min)

Sources & evidence

ORD record
ord-a5e55abde5c74434bb20df2893a5ccc3
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

Loading…