5-fluoro-2,2,7-trimethyl-1-benzofuran-3-one

反応条件: temp:0.00; pressure:0.00; stir:

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: A solution of provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659) (100 mg, 0.515 mmol), N-Bromosuccinimide (100.8 mg, 0.567 mmol), benzoyl chloride (1.2 mg, 0.005 mmol) and carbon tetrachloride (2 mL) was heated at reflux overnight. Saturated sodium bicarbonate was added and extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%) to give 7-(bromomethyl)-5-fluoro-2,2-dimethylbenzofuran-3(2H)-one (660). at reflux overnight extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%)

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

実験手順: To a solution of 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoic acid (658) (5 g, 23.6 mmol) in tetrahydrofuran (50 mL) at 0° C. was added cat. DMF and oxayl chloride (2.5 mL, 28.3 mmol). The reaction was warmed to room temperature, stirred for 1 hour, and concentrated in vacuo. The oil was dissolved in dichloromethane (50 mL), cooled to −78° C. and AlCl3 (7.6 g, 56.6 mmol) was added. The reaction was allowed to warm to room temperature overnight. Ice water was added and the dichloromethane was removed in vacuo. The aqueous phase was extracted with ethyl acetate (3×50 mL) and washed with saturated sodium bicarbonate dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659). concentrated in vacuo The oil was dissolved in dichloromethane (50 mL) cooled to −78° C. to warm to room temperature overnight the dichloromethane was removed in vacuo The aqueous phase was extracted with ethyl acetate (3×50 mL) washed with saturated sodium bicarbonate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%)

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

実験手順: A solution of provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659) (100 mg, 0.515 mmol), N-Bromosuccinimide (100.8 mg, 0.567 mmol), benzoyl chloride (1.2 mg, 0.005 mmol) and carbon tetrachloride (2 mL) was heated at reflux overnight. Saturated sodium bicarbonate was added and extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%) to give 7-(bromomethyl)-5-fluoro-2,2-dimethylbenzofuran-3(2H)-one (660). at reflux overnight extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%)

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

実験手順: To a solution of 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoic acid (658) (5 g, 23.6 mmol) in tetrahydrofuran (50 mL) at 0° C. was added cat. DMF and oxayl chloride (2.5 mL, 28.3 mmol). The reaction was warmed to room temperature, stirred for 1 hour, and concentrated in vacuo. The oil was dissolved in dichloromethane (50 mL), cooled to −78° C. and AlCl3 (7.6 g, 56.6 mmol) was added. The reaction was allowed to warm to room temperature overnight. Ice water was added and the dichloromethane was removed in vacuo. The aqueous phase was extracted with ethyl acetate (3×50 mL) and washed with saturated sodium bicarbonate dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659). concentrated in vacuo The oil was dissolved in dichloromethane (50 mL) cooled to −78° C. to warm to room temperature overnight the dichloromethane was removed in vacuo The aqueous phase was extracted with ethyl acetate (3×50 mL) washed with saturated sodium bicarbonate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%)

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

実験手順: A solution of provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659) (100 mg, 0.515 mmol), N-Bromosuccinimide (100.8 mg, 0.567 mmol), benzoyl chloride (1.2 mg, 0.005 mmol) and carbon tetrachloride (2 mL) was heated at reflux overnight. Saturated sodium bicarbonate was added and extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%) to give 7-(bromomethyl)-5-fluoro-2,2-dimethylbenzofuran-3(2H)-one (660). at reflux overnight extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%)

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

実験手順: To a solution of 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoic acid (658) (5 g, 23.6 mmol) in tetrahydrofuran (50 mL) at 0° C. was added cat. DMF and oxayl chloride (2.5 mL, 28.3 mmol). The reaction was warmed to room temperature, stirred for 1 hour, and concentrated in vacuo. The oil was dissolved in dichloromethane (50 mL), cooled to −78° C. and AlCl3 (7.6 g, 56.6 mmol) was added. The reaction was allowed to warm to room temperature overnight. Ice water was added and the dichloromethane was removed in vacuo. The aqueous phase was extracted with ethyl acetate (3×50 mL) and washed with saturated sodium bicarbonate dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659). concentrated in vacuo The oil was dissolved in dichloromethane (50 mL) cooled to −78° C. to warm to room temperature overnight the dichloromethane was removed in vacuo The aqueous phase was extracted with ethyl acetate (3×50 mL) washed with saturated sodium bicarbonate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%)

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

実験手順: A solution of provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659) (100 mg, 0.515 mmol), N-Bromosuccinimide (100.8 mg, 0.567 mmol), benzoyl chloride (1.2 mg, 0.005 mmol) and carbon tetrachloride (2 mL) was heated at reflux overnight. Saturated sodium bicarbonate was added and extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%) to give 7-(bromomethyl)-5-fluoro-2,2-dimethylbenzofuran-3(2H)-one (660). at reflux overnight extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%)

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

実験手順: To a solution of 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoic acid (658) (5 g, 23.6 mmol) in tetrahydrofuran (50 mL) at 0° C. was added cat. DMF and oxayl chloride (2.5 mL, 28.3 mmol). The reaction was warmed to room temperature, stirred for 1 hour, and concentrated in vacuo. The oil was dissolved in dichloromethane (50 mL), cooled to −78° C. and AlCl3 (7.6 g, 56.6 mmol) was added. The reaction was allowed to warm to room temperature overnight. Ice water was added and the dichloromethane was removed in vacuo. The aqueous phase was extracted with ethyl acetate (3×50 mL) and washed with saturated sodium bicarbonate dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659). concentrated in vacuo The oil was dissolved in dichloromethane (50 mL) cooled to −78° C. to warm to room temperature overnight the dichloromethane was removed in vacuo The aqueous phase was extracted with ethyl acetate (3×50 mL) washed with saturated sodium bicarbonate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%)

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

実験手順: A solution of provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659) (100 mg, 0.515 mmol), N-Bromosuccinimide (100.8 mg, 0.567 mmol), benzoyl chloride (1.2 mg, 0.005 mmol) and carbon tetrachloride (2 mL) was heated at reflux overnight. Saturated sodium bicarbonate was added and extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%) to give 7-(bromomethyl)-5-fluoro-2,2-dimethylbenzofuran-3(2H)-one (660). at reflux overnight extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (5%)

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

実験手順: To a solution of 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoic acid (658) (5 g, 23.6 mmol) in tetrahydrofuran (50 mL) at 0° C. was added cat. DMF and oxayl chloride (2.5 mL, 28.3 mmol). The reaction was warmed to room temperature, stirred for 1 hour, and concentrated in vacuo. The oil was dissolved in dichloromethane (50 mL), cooled to −78° C. and AlCl3 (7.6 g, 56.6 mmol) was added. The reaction was allowed to warm to room temperature overnight. Ice water was added and the dichloromethane was removed in vacuo. The aqueous phase was extracted with ethyl acetate (3×50 mL) and washed with saturated sodium bicarbonate dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659). concentrated in vacuo The oil was dissolved in dichloromethane (50 mL) cooled to −78° C. to warm to room temperature overnight the dichloromethane was removed in vacuo The aqueous phase was extracted with ethyl acetate (3×50 mL) washed with saturated sodium bicarbonate dried over sodium sulfate filtered concentrated in vacuo The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%)