3,4,6-trifluoro-2-methoxybenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3,4,6-trifluoro-2-methoxybenzaldehyde (Preparation 29, 0.118 g, 0.000280 mol) and potassium carbonate (0.097 g, 0.000702 mol) in dimethyl sulfoxide (3.5 mL) was added 4-chloro-3-(trifluoromethyl)phenol (0.0565 g, 0.000287 mol) portion wise. The reaction mixture was stirred at room temperature under nitrogen for 1 hour. The reaction was diluted with ethyl acetate (15.0 mL) and washed twice with water (10.0 mL). The organic layer was separated, dried with sodium sulphate, filtered and concentrated in vacuo. The residue was dissolved in iso-propyl acetate (3.0 mL) and methanesulfonamide (0.0226 g, 0.000238 mol) and bis(tert-butylcarbonyloxy)iodobenzene (0.145 g, 0.000375 mol) were added The mixture was stirred for 5 minutes before the addition of bis[rhodium(alpha, alpha, alpha′, alpha′-tetramethyl-1,3-benzenedipropionic acid)] (0.005 g, 0.00007 mol). The reaction was stirred at 55° C. under nitrogen for 2 hours. The solvent was concentrated in vacuo to afford a crude oil, which was purified using silica gel column chromatography eluting with 0-50% EtOAc in heptanes to furnish a solid. This was further triturated in heptane:acetone (9:1 mixture, 10.0 mL) to yield the title compound as a pale orange solid (0.025 g, 19%). washed twice with water (10.0 mL) The organic layer was separated dried with sodium sulphate filtered concentrated in vacuo The residue was dissolved in iso-propyl acetate (3.0 mL) The reaction was stirred at 55° C. under nitrogen for 2 hours The solvent was concentrated in vacuo to afford a crude oil, which was purified eluting with 0-50% EtOAc in heptanes to furnish a solid This was further triturated in heptane:acetone (9:1 mixture, 10.0 mL)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3,4,6-trifluoro-2-methoxybenzaldehyde (Preparation 29, 0.118 g, 0.000280 mol) and potassium carbonate (0.097 g, 0.000702 mol) in dimethyl sulfoxide (3.5 mL) was added 4-chloro-3-(trifluoromethyl)phenol (0.0565 g, 0.000287 mol) portion wise. The reaction mixture was stirred at room temperature under nitrogen for 1 hour. The reaction was diluted with ethyl acetate (15.0 mL) and washed twice with water (10.0 mL). The organic layer was separated, dried with sodium sulphate, filtered and concentrated in vacuo. The residue was dissolved in iso-propyl acetate (3.0 mL) and methanesulfonamide (0.0226 g, 0.000238 mol) and bis(tert-butylcarbonyloxy)iodobenzene (0.145 g, 0.000375 mol) were added The mixture was stirred for 5 minutes before the addition of bis[rhodium(alpha, alpha, alpha′, alpha′-tetramethyl-1,3-benzenedipropionic acid)] (0.005 g, 0.00007 mol). The reaction was stirred at 55° C. under nitrogen for 2 hours. The solvent was concentrated in vacuo to afford a crude oil, which was purified using silica gel column chromatography eluting with 0-50% EtOAc in heptanes to furnish a solid. This was further triturated in heptane:acetone (9:1 mixture, 10.0 mL) to yield the title compound as a pale orange solid (0.025 g, 19%). washed twice with water (10.0 mL) The organic layer was separated dried with sodium sulphate filtered concentrated in vacuo The residue was dissolved in iso-propyl acetate (3.0 mL) The reaction was stirred at 55° C. under nitrogen for 2 hours The solvent was concentrated in vacuo to afford a crude oil, which was purified eluting with 0-50% EtOAc in heptanes to furnish a solid This was further triturated in heptane:acetone (9:1 mixture, 10.0 mL)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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