反应详情

Paraformaldehyde (0.960 g, 0.01066 mol) and magnesium chloride (0.505 g, 0.005304 mol) were suspended in tetrahydrofuran (10.0 mL). Triethylamine (0.75 mL, 0.0054 mol) was added and the mixture was stirred under nitrogen for 10 minutes. 2,3,5-trifluorophenol (0.524 g, 0.00027 mol) was then added and the reaction mixture was stirred at reflux for 16 hours. The reaction mixture was filtered and the filtrate was diluted with an aqueous solution of hydrochloric acid (2.0 M, 15.0 mL). The product was extracted with tert-butyl methyl ether (20.0 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in dimethylformamide (5.0 mL). Potassium carbonate (0.55 g, 0.003979 mol), followed by 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 with an aqueous solution of saturated brine (15.0 mL) and the product was extracted with tert-butyl methyl ether (20.0 mL). The organic layers were combined, then dried over sodium sulfate, filtered, and concentrated in vacuo. The title compound was purified using silica gel column chromatography (gradient of 0-10% ethyl acetate in heptane, 40 g SiO2) to afford the title compound as a colourless oil (0.080 g, 0.000432 mol, 16%).

1. stirringthe reaction mixture was stirred
2. temperatureat reflux for 16 hours
3. filtrationThe reaction mixture was filtered
4. additionthe filtrate was diluted with an aqueous solution of hydrochloric acid (2.0 M, 15.0 mL)
5. extractionThe product was extracted with tert-butyl methyl ether (20.0 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in dimethylformamide (5.0 mL)
10. additionwere added to the mixture, which
11. stirringwas stirred at 50° C. under nitrogen for 3 hours
12. waitleft
13. stirringto stir at room temperature for 72 hours
14. extractionthe product was extracted with tert-butyl methyl ether (20.0 mL)
15. dry with materialdried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customThe title compound was purified