反应详情

Paraformaldehyde (0.960 g, 0.01066 mol) and magnesium dichloride (0.505 g, 0.005304 mol) were suspended in THF (10.0 mL). Triethylamine (0.75 mL, 0.0054 mol) was added and the mixture was stirred under nitrogen for 10 minutes. Then 2,3,5-trifluorophenol (0.524 g, 0.00027 mol) was added and the reaction mixture was stirred at refluxed for 16 hours. The reaction mixture was subjected to filtration and the filtrate was diluted with an aqueous solution of hydrochloric acid (2.0 M, 15 mL). The product was then extracted with tert-butyl methyl ether (20 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude was dissolved in DMF (5.0 mL). Then potassium carbonate (0.55 g, 0.003979 mol) and methyl iodide (0.175 mL, 0.00072 mol) were added to the mixture, which was stirred at 50° C. under nitrogen for 3 hours, then left to stir at room temperature for 72 hours. The reaction was diluted in an aqueous solution of saturated brine (15 mL) and extracted with tert-butyl methyl ether (20 mL). The organics were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude was purified by silica gel chromatography eluting with 0 to 10% EtOAc in heptane to yield the title compound as a colourless oil (0.080 g, 0.432 mmol).

1. stirringthe reaction mixture was stirred
2. temperatureat refluxed for 16 hours
3. filtrationThe reaction mixture was subjected to filtration
4. additionthe filtrate was diluted with an aqueous solution of hydrochloric acid (2.0 M, 15 mL)
5. extractionThe product was then extracted with tert-butyl methyl ether (20 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. dissolutionThe crude was dissolved in DMF (5.0 mL)
10. stirringwas stirred at 50° C. under nitrogen for 3 hours
11. waitleft
12. stirringto stir at room temperature for 72 hours
13. extractionextracted with tert-butyl methyl ether (20 mL)
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe resulting crude was purified by silica gel chromatography
18. washeluting with 0 to 10% EtOAc in heptane