2-fluoro-5-iodophenol

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add bis(phenylnitrile)palladium (II) chloride (115 mg, 0.3 mmol) to a suspension of copper (I) iodide (38 mg, 0.2 mmol) in anhydrous 1,4-dioxane (1 mL) under nitrogen and stir for 10 min. Sequentially add 5-ethynyl-nicotinonitrile (1.28 g, 10 mmol), (prepared essentially as described in PREPARATION 4), 2-fluoro-5-iodophenol, (prepared essentially as described in PREPARATION 15), (2.37 g, 10 mmol) and tri-tert-butylphosphine (121 mg, 0.6 mmol) in 1,4-dioxane (5 mL) and diethylamine (2.1 mL, 12 mmol) to the reaction mixture and heat at 60° C. for 16 h. Cool to room temperature, dilute with diethyl ether, stir for 10 min and filter through diatomaceous earth. Wash the filtrate sequentially with water and an aqueous saturated solution of sodium chloride. Dry (magnesium sulfate), concentrate and purify by silica gel chromatography, eluting with 0:100 to 35:100 ethyl acetate:hexanes, to give the title compound (1.0 g, 42%) as a yellow solid. (prepared essentially Cool to room temperature stir for 10 min filter through diatomaceous earth Wash the filtrate sequentially with water Dry (magnesium sulfate) concentrate purify by silica gel chromatography eluting with 0:100 to 35:100 ethyl acetate

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

実験手順: To a cooled solution of 2-fluoro-5-iodophenylboronic acid in tetrahydrofuran (200 mL) at 0° C. add an aqueous solution of 30% hydrogen peroxide (9.92 mL, 103 mmol) dropwise, stir 10 min, and add an aqueous 4 N solution of sodium hydroxide (1.78 mL, 7.12 mmol). Warm the reaction to room temperature and stir overnight. Add manganese dioxide (250 mg) to the reaction, stir 90 min and filter through fluted filter paper. Concentrate and partition the residue between diethyl ether and water. Separate the layers and sequentially wash the organic layer with water and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter and concentrate. Purify the resulting tan oil by silica gel chromatography, eluting with a gradient of 0:100 to 30:70 ethyl acetate:hexanes, to give the title compound as a yellow waxy solid (18.1 g, 65%). Warm the reaction to room temperature stir overnight stir 90 min filter through fluted filter paper Concentrate partition the residue between diethyl ether and water Separate the layers sequentially wash the organic layer with water Dry (sodium sulfate) filter concentrate Purify the resulting tan oil by silica gel chromatography eluting with a gradient of 0:100 to 30:70 ethyl acetate

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add bis(phenylnitrile)palladium (II) chloride (115 mg, 0.3 mmol) to a suspension of copper (I) iodide (38 mg, 0.2 mmol) in anhydrous 1,4-dioxane (1 mL) under nitrogen and stir for 10 min. Sequentially add 5-ethynyl-nicotinonitrile (1.28 g, 10 mmol), (prepared essentially as described in PREPARATION 4), 2-fluoro-5-iodophenol, (prepared essentially as described in PREPARATION 15), (2.37 g, 10 mmol) and tri-tert-butylphosphine (121 mg, 0.6 mmol) in 1,4-dioxane (5 mL) and diethylamine (2.1 mL, 12 mmol) to the reaction mixture and heat at 60° C. for 16 h. Cool to room temperature, dilute with diethyl ether, stir for 10 min and filter through diatomaceous earth. Wash the filtrate sequentially with water and an aqueous saturated solution of sodium chloride. Dry (magnesium sulfate), concentrate and purify by silica gel chromatography, eluting with 0:100 to 35:100 ethyl acetate:hexanes, to give the title compound (1.0 g, 42%) as a yellow solid. (prepared essentially Cool to room temperature stir for 10 min filter through diatomaceous earth Wash the filtrate sequentially with water Dry (magnesium sulfate) concentrate purify by silica gel chromatography eluting with 0:100 to 35:100 ethyl acetate

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

実験手順: To a cooled solution of 2-fluoro-5-iodophenylboronic acid in tetrahydrofuran (200 mL) at 0° C. add an aqueous solution of 30% hydrogen peroxide (9.92 mL, 103 mmol) dropwise, stir 10 min, and add an aqueous 4 N solution of sodium hydroxide (1.78 mL, 7.12 mmol). Warm the reaction to room temperature and stir overnight. Add manganese dioxide (250 mg) to the reaction, stir 90 min and filter through fluted filter paper. Concentrate and partition the residue between diethyl ether and water. Separate the layers and sequentially wash the organic layer with water and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter and concentrate. Purify the resulting tan oil by silica gel chromatography, eluting with a gradient of 0:100 to 30:70 ethyl acetate:hexanes, to give the title compound as a yellow waxy solid (18.1 g, 65%). Warm the reaction to room temperature stir overnight stir 90 min filter through fluted filter paper Concentrate partition the residue between diethyl ether and water Separate the layers sequentially wash the organic layer with water Dry (sodium sulfate) filter concentrate Purify the resulting tan oil by silica gel chromatography eluting with a gradient of 0:100 to 30:70 ethyl acetate