Cyclobutanone → HCID 18779841, compound

Temperature

-78 °C

3-Cyano-1-(2,2-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (500 mg, 1.16 mmol, WO9707102) was dissolved in THF (10 ml) in a dry, nitrogen-flushed flask and cooled to -78° C. n-Butyllithium 0.46 ml, 2.5M in hexanes) was added dropwise over a period of 30 min, keeping the internal temperature at ca. -72° C. The reaction mixture was stirred at -78° C. for 20 min. then cyclobutanone (0.10 ml, 1.28 mmol), dissolved in THF (4 ml), was added dropwise and the mixture was stirred for 1 hr at -78° C. before warming to -20° C. After 2 hr, the mixture was warmed to room temperature and stirred overnight. The reaction mixture was poured into aqueous ammonium chloride (20 ml) and extracted with diethyl ether (2×20 ml). The combined organics were washed (brine), dried (Na2SO4), filtered and the solvents removed in vacuo to leave a yellow oil. This was purified by silica chromatography (eluting with a solvent gradient of DCM to 3% methanol/DCM) to yield 256 mg as a clear gum.

1. customflushed flask
2. additionwas added dropwise over a period of 30 min
3. customat ca. -72° C
4. additionwas added dropwise
5. stirringthe mixture was stirred for 1 hr at -78° C.
6. temperaturebefore warming to -20° C
7. waitAfter 2 hr
8. temperaturethe mixture was warmed to room temperature
9. stirringstirred overnight
10. extractionextracted with diethyl ether (2×20 ml)
11. washThe combined organics were washed (brine)
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. customthe solvents removed in vacuo
15. customto leave a yellow oil
16. customThis was purified by silica chromatography (
17. washeluting with a solvent gradient of DCM to 3% methanol/DCM)
18. customto yield 256 mg as a clear gum

ORD record

ord-4d1bc353fdbe4220a3708f503a6c0e4d

Source dataset

uspto-grants-2000_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06077859