反応 #74676

反応方程式

Cesium fluoride

5-fluoro-2-iodo-4-(trifluoromethyl)phenol

4-(tributylstannyl)pyridazine

N,N-dimethylformamide

N,N-dimethylformamide

→

product

収率 62.5%

5-Fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol

収率 62.5%

反応条件

後処理

1. 1
   その他The flask was capped with a septum
2. 2
   その他then evacuated
3. 3
   workup.ADDITIONback-filled with argon (5 cycles)
4. 4
   温度the reaction mixture was cooled to ambient temperature
5. 5
   workup.ADDITIONdiluted with ethyl acetate and water
6. 6
   ろ過filtered through diatomaceous earth
7. 7
   洗浄The solids were washed with additional ethyl acetate
8. 8
   その他The layers were separated
9. 9
   洗浄the organic layer was washed successively with water, aqueous lithium chloride, and brine
10. 10
    乾燥The organic layer was then dried over sodium sulfate
11. 11
    ろ過filtered
12. 12
    濃縮concentrated in vacuo
13. 13
    濃縮concentrated onto diatomaceous earth
14. 14
    その他purified by automated flash chromatography (24 g SiO2, methylene chloride to 9:1 methylene chloride-methanol)

実験手順

Cesium fluoride (570 mg, 3.8 mmol), tetrakis(triphenylphosphine)palladium(0) (220 mg, 0.19 mmol), and copper(I) iodide (72 mg, 0.38 mmol) were added to a solution of 5-fluoro-2-iodo-4-(trifluoromethyl)phenol (Preparation 885, 579 mg, 1.89 mmol) and 4-(tributylstannyl)pyridazine (770 mg, 2.1 mmol) in N,N-dimethylformamide (4 mL, 50 mmol). The sides of the flask were washed down with N,N-dimethylformamide (3 mL, 40 mmol). The flask was capped with a septum then evacuated and back-filled with argon (5 cycles). The reaction mixture was heated at 45° C. After 90 min, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and water, and filtered through diatomaceous earth. The solids were washed with additional ethyl acetate. The layers were separated, and the organic layer was washed successively with water, aqueous lithium chloride, and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in methylene chloride, concentrated onto diatomaceous earth, and purified by automated flash chromatography (24 g SiO2, methylene chloride to 9:1 methylene chloride-methanol) to afford the product as a tan solid (305 mg, 62%).

出典