Acetic Acid → 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzonitrile

HRID 1773083Notes

Reaction equation

HRID 1773083 reaction equation
C(O)(=O)C.OO.[CH:7]1([C:10]2[N:11]=[C:12](S)[N:13]([C:15]3[C:16]([CH3:24])=[CH:17][C:18]([F:23])=[C:19]([CH:22]=3)[C:20]#[N:21])[CH:14]=2)[CH2:9][CH2:8]1.S([O-])([O-])=O.[Na+].[Na+]>O>[CH:7]1([C:10]2[N:11]=[CH:12][N:13]([C:15]3[C:16]([CH3:24])=[CH:17][C:18]([F:23])=[C:19]([CH:22]=3)[C:20]#[N:21])[CH:14]=2)[CH2:8][CH2:9]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 178427859HCID 178427859, compound

Product 1

HCID 866912495-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
45 °C

Procedure

In a 500 mL three neck round bottom flask was placed acetic acid (96 mL), water (19 mL) and hydrogen peroxide (30%, 7.47 mL, 65.88 mmol). The mixture was heated to 45° C. with stirring under nitrogen while monitoring the internal temperature. 5-(4-Cyclopropyl-2-mercapto-1H-imidazol-1-yl)-2-fluoro-4-methylbenzonitrile (6.00 g, 21.96 mmol) was then added as a solid in small portions over 30 minutes while maintaining an internal temperature below 55° C. When addition of the thioimidazole was complete the reaction was stirred for 30 minutes at a temperature of 45° C., and then cooled to room temperature, and a solution of 20% wt/wt sodium sulfite in water (6 mL) was slowly added. The mixture was stirred for 30 minutes and solvents were removed under reduced pressure. The residue was suspended in 250 mL of water and 4N aqueous ammonium hydroxide was added to bring the pH to ˜10. The mixture was extracted with dichloromethane (3×200 ml), the organics combined, dried over magnesium sulfate, and the solvent was removed under reduced pressure. The residue was dissolved in 20 mL EA, and 80 mL of hexanes were added with stirring. The solvents were decanted off and an oily residue was left behind. This process was repeated and the product, 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzonitrile was obtained as a viscous oil (5.14 g, 21.33 mmol) Anal. LC/MS (m/z: 242, M+1)

Workup

  1. temperaturewhile maintaining an internal temperature below 55° C
  2. stirringwas stirred for 30 minutes at a temperature of 45° C.
  3. temperaturecooled to room temperature
  4. stirringThe mixture was stirred for 30 minutes
  5. customsolvents were removed under reduced pressure
  6. addition4N aqueous ammonium hydroxide was added
  7. extractionThe mixture was extracted with dichloromethane (3×200 ml)
  8. dry with materialdried over magnesium sulfate
  9. customthe solvent was removed under reduced pressure
  10. dissolutionThe residue was dissolved in 20 mL EA
  11. addition80 mL of hexanes were added
  12. stirringwith stirring
  13. customThe solvents were decanted off
  14. waitan oily residue was left behind

Sources & evidence

ORD record
ord-ab9bdd073dee40e19e44ac736705257f
Source dataset
uspto-grants-2016_02
Patent number
US09254284B2

Reaction notes

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