反应详情

温度

2.5 °C

1-(3′,4′-dichloro-2-fluoro[1,1′-biphenyl]-4-yl)-cyclopropanenitrile (14.3 g, 0.047 mol) is dissolved in a mixture of methanol (143 ml) and water (71.5 ml), potassium hydroxide (35.1 g, 0.563 mol) is added portionwise, and the mixture is refluxed for 48 hours. The reaction mixture is cooled and poured into a solution of aqueous hydrogen chloride 36% (57 ml) in water (57 ml) at 20-25° C. The suspension is stirred and filtered; the solid is repeatedly washed with water and dried at 40° C. under vacuum. The crude product is dissolved in refluxing 2-propanol (178 ml), the solution is mixed with activated carbon (0.3 g), stirred at reflux and filtered, concentrated and mixed with n-heptane (116 ml). The hot solution is cooled to 0 to 5° C. and the crystallized solid is filtered, washed with 2-propanol and dried at 40° C. under vacuum. The compound 1-(3′,4′-dichloro-2-fluoro[1,1′-biphenyl]-4-yl)-cyclopropanecarboxylic acid is obtained as a white powder (10.3 g, 68% yield).

1. additionis added portionwise
2. temperaturethe mixture is refluxed for 48 hours
3. temperatureThe reaction mixture is cooled
4. filtrationfiltered
5. washthe solid is repeatedly washed with water
6. customdried at 40° C. under vacuum
7. dissolutionThe crude product is dissolved
8. temperaturein refluxing 2-propanol (178 ml)
9. additionthe solution is mixed with activated carbon (0.3 g)
10. stirringstirred
11. temperatureat reflux
12. filtrationfiltered
13. concentrationconcentrated
14. additionmixed with n-heptane (116 ml)
15. filtrationthe crystallized solid is filtered
16. washwashed with 2-propanol
17. customdried at 40° C. under vacuum