4-chloro-5-fluoro-2-iodophenol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Fluoro-4-chlorophenol (1.78 g, 12.1 mmol) was dissolved in methanol (40 mL). Sodium iodide (3.63 g, 24.2 mmol) and sodium hydroxide (0.97 g, 24.2 mmol) was added, and the solution was cooled to 0° C. Aqueous sodium hypochlorite (6.0% NaOCl, 24.2 mmol) was added dropwise over 75 minutes at 0-3° C. The resulting slurry was stirred for 1 h at 0-2° C. and allowed to warm up to room temperature overnight. White precipitates were observed. The mixture was adjusted to pH 7 using 1M aqueous HCl while stirring. The aqueous layer was extracted with ether for three times and the ether layer was washed with aq sodium thiosulfate, brine, the organic layers were dried with MgSO4. The solvent was removed under reduced pressure to afford the residue which was purified by flash column chromatography on silica gel (Hexanes:Ethyl acetate 1:1 to afford the desired product (1.60 g, 64% yield). 1H NMR: 6.84 (d, 1H, J=9.9 Hz), 7.67 (d, 1H, J=8.1 Hz). to warm up to room temperature overnight White precipitates while stirring The aqueous layer was extracted with ether for three times the ether layer was washed with aq sodium thiosulfate, brine the organic layers were dried with MgSO4 The solvent was removed under reduced pressure to afford the residue which was purified by flash column chromatography on silica gel (Hexanes:Ethyl acetate 1:1

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

実験手順: To a suspension of N-iodosuccinamide (6.1 g, 27.3 mmol) in glacial acetic acid (23 mL) was added 4-chloro-3-fluorophenol (4.0 g, 27.3 mmol) and after 5 minutes sulphuric acid was added (0.5 mL, 8.2 mmol) and the reaction mixture was left to stir at room temperature for 16 hours. The reaction was quenched by addition of water (30 mL) and the compound was extracted into dichloromethane (3×30 mL). The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL), then saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and evaporated in vacuo. The crude material was purified by flash column chromatography (silica, toluene) to afford the desired product as an oil (4.0 g, 54%). the reaction mixture was left The reaction was quenched by addition of water (30 mL) the compound was extracted into dichloromethane (3×30 mL) The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL) saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate filtered evaporated in vacuo The crude material was purified by flash column chromatography (silica, toluene)

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

実験手順: Prepared using the method of Example 587 using 4-chloro-5-fluoro-2-iodophenol (Preparation 744, 386 mg, 1.42 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (500 mg, 1.70 mmol) gave the title compound as a white solid (200 mg, 38%). Prepared

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a suspension of N-iodosuccinamide (6.1 g, 27.3 mmol) in glacial acetic acid (23 mL) was added 4-chloro-3-fluorophenol (4.0 g, 27.3 mmol) and after 5 minutes sulphuric acid was added (0.5 mL, 8.2 mmol) and the reaction mixture was left to stir at room temperature for 16 hours. The reaction was quenched by addition of water (30 mL) and the compound was extracted into dichloromethane (3×30 mL). The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL), then saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and evaporated in vacuo. The crude material was purified by flash column chromatography (silica, toluene) to afford the desired product as an oil (4.0 g, 54%). the reaction mixture was left The reaction was quenched by addition of water (30 mL) the compound was extracted into dichloromethane (3×30 mL) The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL) saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate filtered evaporated in vacuo The crude material was purified by flash column chromatography (silica, toluene)

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

実験手順: Prepared using the method of Example 587 using 4-chloro-5-fluoro-2-iodophenol (Preparation 744, 386 mg, 1.42 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (500 mg, 1.70 mmol) gave the title compound as a white solid (200 mg, 38%). Prepared

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

実験手順: To a suspension of N-iodosuccinamide (6.1 g, 27.3 mmol) in glacial acetic acid (23 mL) was added 4-chloro-3-fluorophenol (4.0 g, 27.3 mmol) and after 5 minutes sulphuric acid was added (0.5 mL, 8.2 mmol) and the reaction mixture was left to stir at room temperature for 16 hours. The reaction was quenched by addition of water (30 mL) and the compound was extracted into dichloromethane (3×30 mL). The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL), then saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and evaporated in vacuo. The crude material was purified by flash column chromatography (silica, toluene) to afford the desired product as an oil (4.0 g, 54%). the reaction mixture was left The reaction was quenched by addition of water (30 mL) the compound was extracted into dichloromethane (3×30 mL) The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL) saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate filtered evaporated in vacuo The crude material was purified by flash column chromatography (silica, toluene)

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

実験手順: Prepared using the method of Example 587 using 4-chloro-5-fluoro-2-iodophenol (Preparation 744, 386 mg, 1.42 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (500 mg, 1.70 mmol) gave the title compound as a white solid (200 mg, 38%). Prepared

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

実験手順: To a suspension of N-iodosuccinamide (6.1 g, 27.3 mmol) in glacial acetic acid (23 mL) was added 4-chloro-3-fluorophenol (4.0 g, 27.3 mmol) and after 5 minutes sulphuric acid was added (0.5 mL, 8.2 mmol) and the reaction mixture was left to stir at room temperature for 16 hours. The reaction was quenched by addition of water (30 mL) and the compound was extracted into dichloromethane (3×30 mL). The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL), then saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and evaporated in vacuo. The crude material was purified by flash column chromatography (silica, toluene) to afford the desired product as an oil (4.0 g, 54%). the reaction mixture was left The reaction was quenched by addition of water (30 mL) the compound was extracted into dichloromethane (3×30 mL) The combined organic layers were washed with 10% sodium metabisulphite aqueous solution (2×20 mL) saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate filtered evaporated in vacuo The crude material was purified by flash column chromatography (silica, toluene)

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

実験手順: Prepared using the method of Example 587 using 4-chloro-5-fluoro-2-iodophenol (Preparation 744, 386 mg, 1.42 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (500 mg, 1.70 mmol) gave the title compound as a white solid (200 mg, 38%). Prepared

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Fluoro-4-chlorophenol (1.78 g, 12.1 mmol) was dissolved in methanol (40 mL). Sodium iodide (3.63 g, 24.2 mmol) and sodium hydroxide (0.97 g, 24.2 mmol) was added, and the solution was cooled to 0° C. Aqueous sodium hypochlorite (6.0% NaOCl, 24.2 mmol) was added dropwise over 75 minutes at 0-3° C. The resulting slurry was stirred for 1 h at 0-2° C. and allowed to warm up to room temperature overnight. White precipitates were observed. The mixture was adjusted to pH 7 using 1M aqueous HCl while stirring. The aqueous layer was extracted with ether for three times and the ether layer was washed with aq sodium thiosulfate, brine, the organic layers were dried with MgSO4. The solvent was removed under reduced pressure to afford the residue which was purified by flash column chromatography on silica gel (Hexanes:Ethyl acetate 1:1 to afford the desired product (1.60 g, 64% yield). 1H NMR: 6.84 (d, 1H, J=9.9 Hz), 7.67 (d, 1H, J=8.1 Hz). to warm up to room temperature overnight White precipitates while stirring The aqueous layer was extracted with ether for three times the ether layer was washed with aq sodium thiosulfate, brine the organic layers were dried with MgSO4 The solvent was removed under reduced pressure to afford the residue which was purified by flash column chromatography on silica gel (Hexanes:Ethyl acetate 1:1