反应详情

温度

45 °C

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)

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