Hydrochloric Acid → Chf-5074

Temperature

2.5 °C

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

1. additionwas added portion-wise
2. temperaturethe mixture was refluxed for 48 hours
3. temperatureThe reaction mixture was cooled
4. filtrationfiltered
5. washthe solid was repeatedly washed with water
6. customdried at 40° C. under vacuum
7. dissolutionThe crude product was dissolved
8. temperaturein refluxing 2-propanol (178 ml)
9. additionthe solution was 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 was filtered
16. washwashed with 2-propanol
17. customdried at 40° C. under vacuum

ORD record

ord-0ec6cff9a55447c9bde5c621e3f017a7

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08076505B2