Water → HCID 9907479, compound

Temperature

-5 °C

Methyltriphenylphosphonium bromide (304 mg, 0.85 mmol) was suspended in dry diethyl ether (5 ml) in a nitrogen-flushed flask and cooled to -5° C. n-Butyl lithium (0.34 ml, 2.5M in hexanes) was added dropwise producing a yellow colour. The mixture was warmed to room temperature before heating to reflux for 1 hr. The amber homogeneous solution thus obtained was cooled to -78° C. and 3-cyano-4-(3-oxocyclobutyl)-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole (300 mg, 0.80 mmol, Example 3), dissolved in dry diethyl ether (5 ml), added dropwise keeping the internal temperature at ca. -70° C. The mixture was allowed to slowly warm to room temperature before refluxing for 1 hr. The mixture was then cooled, poured into water (20 ml) and extracted with diethyl ether (3×10 ml). The combined organics were washed with brine, dried (MgSO4), filtered and ether solvent evaporated in vacuo. The residue was purified by silica chromatography (eluting with 20% DCM/hexane) yielding 40 mg of a white solid. This was further purified by hplc (Microsorb™C18, eluting with acetonitrile/methanol/water 6:1:3 v/v) to give 18 mg of the title compound.

1. customflushed flask
2. additionwas added dropwise
3. customproducing a yellow colour
4. temperatureThe mixture was warmed to room temperature
5. temperaturebefore heating
6. temperatureto reflux for 1 hr
7. customThe amber homogeneous solution thus obtained
8. temperaturewas cooled to -78° C.
9. additionadded dropwise
10. customat ca. -70° C
11. temperatureto slowly warm to room temperature
12. temperaturebefore refluxing for 1 hr
13. temperatureThe mixture was then cooled
14. extractionextracted with diethyl ether (3×10 ml)
15. washThe combined organics were washed with brine
16. dry with materialdried (MgSO4)
17. filtrationfiltered
18. customether solvent evaporated in vacuo
19. customThe residue was purified by silica chromatography (eluting with 20% DCM/hexane)

ORD record

ord-6b9034641c094168b909f21da9188e84

Source dataset

uspto-grants-2000_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06077859