反应详情

温度

0 °C

A suspension of 2-(4-fluorophenyl)-1-[4-(methylthio)phenyl]ethanone from Step 1 (11.53 g. 44 mmol) in 225 mL dry tetrahydrofuran (THF) was treated with 52.8 mL lithium bis(trimethylsilyl) amide (1.0M in THF) at -70° C. under nitrogen for 30 minutes and warmed to 0° C. for 30 minutes. Upon cooling to -70° C., a solution of 10.0 g (61 mmol) 1-trifluoroacetylimidazole in 25 mL THF was added and the mixture warmed to 0° C., during which time the solids dissolved. After 45 minutes, the reaction was quenched with saturated aqueous NH4Cl. The organic layer was diluted with ethyl acetate, washed sequentially with dilute HCl and brine, dried over MgSO4 and concentrated in vacuo. The crude mixture was washed with ether to remove unreacted starting ketone and the yellow solid (11.3 g) used without further purification. The crude mixture (11.3 g) was stirred with 60 mL glacial acetic acid and 4.5 mL hydrazine hydrane at reflux under nitrogen for 18 hours. The acetic acid was then removed in vacuo, and the residue dissolved in ethyl acetate, washed sequentially with dilute HCl and brine, dried over MgSO4 and reconcentrated in vacuo. Recrystallization from chloroform-hexane gave 8.24 g of the pyrazole as a pale yellow solid. Elemental analysis for C17H12N2F4S Calc'd.: C, 57.95, H, 3.43, N, 7.95, S, 9.10. Found: C, 57.58, H, 3.50, N, 7.88, S, 8.97.

1. temperatureUpon cooling to -70° C.
2. temperaturethe mixture warmed to 0° C., during which time the solids
3. dissolutiondissolved
4. customthe reaction was quenched with saturated aqueous NH4Cl
5. additionThe organic layer was diluted with ethyl acetate
6. washwashed sequentially with dilute HCl and brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. washThe crude mixture was washed with ether
10. customto remove unreacted
11. customthe yellow solid (11.3 g) used without further purification
12. temperatureat reflux under nitrogen for 18 hours
13. customThe acetic acid was then removed in vacuo
14. dissolutionthe residue dissolved in ethyl acetate
15. washwashed sequentially with dilute HCl and brine
16. dry with materialdried over MgSO4
17. customRecrystallization from chloroform-hexane