2,3,5-三氟苯酚

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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%). the reaction mixture was stirred at reflux for 16 hours The reaction mixture was filtered 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 concentrated in vacuo The residue was dissolved in dimethylformamide (5.0 mL) were added to the mixture, which was stirred at 50° C. under nitrogen for 3 hours left to stir at room temperature for 72 hours the product was extracted with tert-butyl methyl ether (20.0 mL) dried over sodium sulfate filtered concentrated in vacuo The title compound was purified

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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). the reaction mixture was stirred at refluxed for 16 hours The reaction mixture was subjected to filtration 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 concentrated in vacuo The crude was dissolved in DMF (5.0 mL) was stirred at 50° C. under nitrogen for 3 hours left to stir at room temperature for 72 hours extracted with tert-butyl methyl ether (20 mL) dried over sodium sulfate filtered concentrated in vacuo The resulting crude was purified by silica gel chromatography eluting with 0 to 10% EtOAc in heptane