Diethyl Ether → 5-Amino-4-(2-chlorophenyl)-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

To a rapidly stirred solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (0.31 g) in toluene (2 ml) containing tetrakis(triphenylphosphine)palladium(0) (0.03 g) was added saturated aqueous sodium hydrogen carbonate solution (3 ml) and a solution of 2-chlorophenylboronic acid (0.45 g) in ethanol (1 ml). The mixture was heated under reflux for 3.5 hours, cooled and then poured into ether (50 ml) and water (50 ml). The layers were separated and the aqueous phase extracted with a second portion of ether (50 ml). The combined organic layers were washed with water (2×50 ml), brine (50 ml) and then dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel (50 g) eluted with dichloromethane. After combination and evaporation of suitable fractions the residue was further purified by HPLC. Combination and processing of suitable fractions gave the title compound as a pale brown crystalline solid, m.p. 192-3° C.

1. temperatureThe mixture was heated
2. temperatureunder reflux for 3.5 hours
3. temperaturecooled
4. customThe layers were separated
5. extractionthe aqueous phase extracted with a second portion of ether (50 ml)
6. washThe combined organic layers were washed with water (2×50 ml), brine (50 ml)
7. dry with materialdried (Na2SO4)
8. customevaporated
9. customThe residue was purified by column chromatography on silica gel (50 g)
10. washeluted with dichloromethane
11. customAfter combination and evaporation of suitable fractions the residue
12. customwas further purified by HPLC

ORD record

ord-3c4d0017aa494fe483040499ace8c97f

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06069157