2-methyl-1-benzofuran

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: Tin tetrachloride (1.15 ml) was added to a solution of 6-bromohexanoyl chloride (2 g) and 2-methylbenzo[b]furan (1.24 g) in carbon disulfide (30 ml) under ice-cooling, the mixture was stirred at room temperature for 3 hr. Ice water and conc. hydrochloric acid were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 2.2 g of 6-bromo-1-(2-methyl-3-benzo[b]furyl)-1-hexanone. cooling the mixture was extracted with ethyl acetate The organic layer was washed with water and brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

実験手順: is obtained as described in Example 1 from 10.1 g 4-chloro-3-sulfamoylbenzoyl chloride and 5.8 g 2-methylbenzo[b]furan in the presence of 11.4 g aluminum chloride. After evaporation of the extraction agent, the residue is stirred with di-isopropyl ether, and the solids are filtered off. Colorless crystals, m.p. 183° C. (from methanol). is obtained After evaporation of the extraction agent the solids are filtered off

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

実験手順: is obtained as described in Example 1 from 10.1 g 4-chloro-3-sulfamoylbenzoyl chloride and 5.8 g 2-methylbenzo[b]furan in the presence of 11.4 g aluminum chloride. After evaporation of the extraction agent, the residue is stirred with di-isopropyl ether, and the solids are filtered off. Colorless crystals, m.p. 183° C. (from methanol). is obtained After evaporation of the extraction agent the solids are filtered off

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyl lithium (0.246 mL, 1.6 M in hexanes) was added to a solution of diisopropyl amine (0.055 mL, 0.45 mmol) in anhydrous THF (5 mL) at 0° C. The reaction mixture was cooled to −78° C. and stirred for 15 minutes. A solution of 2-methylbenzofuran (48 mg, 0.4 mmol) in 2 mL anhydrous THF was added dropwise to this mixture. After the addition, the reaction mixture was stirred for 15 to 30 minutes. 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (100 mg, 0.4 mmol) (Example 1) was added as a solution in anhydrous THF (2 mL) in one portion, the cold bath was removed, and the reaction was stirred at room temperature for 12 hours. THF was evaporated under reduced pressure. Water (2 mL) was added to the residue and the mixture was extracted with three 5 mL portions of EtOAc. The extract was dried over magnesium sulfate. After evaporation, the residue was chromatographed on a silica gel column to provide 86 mg of the title compound as an oil. After the addition the reaction mixture was stirred for 15 to 30 minutes the cold bath was removed the reaction was stirred at room temperature for 12 hours THF was evaporated under reduced pressure Water (2 mL) was added to the residue the mixture was extracted with three 5 mL portions of EtOAc The extract was dried over magnesium sulfate After evaporation the residue was chromatographed on a silica gel column

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

実験手順: A suspension of 2-methylbenzofuran (0.708 g) and N-bromosuccinimide (0.963 g) in carbon tetrachloride (10 ml) was heated at reflux temperature for 2.5 hours. To the mixture was added 2,2'-azobis(isobutyronitrile) (0.1 g) and heated at the same temperature for additional 1 hour. The reaction mixture was allowed to cool to room temperature. The resultant precipitates were filtered off by suction. The filtrate was concentrated in vacuo to give 2-bromomethylbenzofuran (1.16 g), which was used in a following reaction step without further purification. was heated at reflux temperature for 2.5 hours heated at the same temperature for additional 1 hour The resultant precipitates were filtered off by suction The filtrate was concentrated in vacuo

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

実験手順: Tin tetrachloride (1.15 ml) was added to a solution of 6-bromohexanoyl chloride (2 g) and 2-methylbenzo[b]furan (1.24 g) in carbon disulfide (30 ml) under ice-cooling, the mixture was stirred at room temperature for 3 hr. Ice water and conc. hydrochloric acid were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 2.2 g of 6-bromo-1-(2-methyl-3-benzo[b]furyl)-1-hexanone. cooling the mixture was extracted with ethyl acetate The organic layer was washed with water and brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

実験手順: Tin tetrachloride (1.15 ml) was added to a solution of 6-bromohexanoyl chloride (2 g) and 2-methylbenzo[b]furan (1.24 g) in carbon disulfide (30 ml) under ice-cooling, the mixture was stirred at room temperature for 3 hr. Ice water and conc. hydrochloric acid were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 2.2 g of 6-bromo-1-(2-methyl-3-benzo[b]furyl)-1-hexanone. cooling the mixture was extracted with ethyl acetate The organic layer was washed with water and brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

実験手順: is obtained as described in Example 1 from 10.1 g 4-chloro-3-sulfamoylbenzoyl chloride and 5.8 g 2-methylbenzo[b]furan in the presence of 11.4 g aluminum chloride. After evaporation of the extraction agent, the residue is stirred with di-isopropyl ether, and the solids are filtered off. Colorless crystals, m.p. 183° C. (from methanol). is obtained After evaporation of the extraction agent the solids are filtered off

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyl lithium (0.246 mL, 1.6 M in hexanes) was added to a solution of diisopropyl amine (0.055 mL, 0.45 mmol) in anhydrous THF (5 mL) at 0° C. The reaction mixture was cooled to −78° C. and stirred for 15 minutes. A solution of 2-methylbenzofuran (48 mg, 0.4 mmol) in 2 mL anhydrous THF was added dropwise to this mixture. After the addition, the reaction mixture was stirred for 15 to 30 minutes. 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4methylpentan-2-one (100 mg, 0.4 mmol) (Example 1) was added as a solution in anhydrous THF (2 mL) in one portion, the cold bath was removed, and the reaction was stirred at room temperature for 12 hours. THF was evaporated under reduced pressure. Water (2 mL) was added to the residue and the mixture was extracted with three 5 mL portions of EtOAc. The extract was dried over magnesium sulfate. After evaporation, the residue was chromatographed on a silica gel column to provide 86 mg of the title compound as an oil. After the addition the reaction mixture was stirred for 15 to 30 minutes the cold bath was removed the reaction was stirred at room temperature for 12 hours THF was evaporated under reduced pressure Water (2 mL) was added to the residue the mixture was extracted with three 5 mL portions of EtOAc The extract was dried over magnesium sulfate After evaporation the residue was chromatographed on a silica gel column

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyl lithium (0.246 mL, 1.6 M in hexanes) was added to a solution of diisopropyl amine (0.055 mL, 0.45 mmol) in anhydrous THF (5 mL) at 0° C. The reaction mixture was cooled to −78° C. and stirred for 15 minutes. A solution of 2-methylbenzofuran (48 mg, 0.4 mmol) in 2 mL anhydrous THF was added dropwise to this mixture. After the addition, the reaction mixture was stirred for 15 to 30 minutes. 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (100 mg, 0.4 mmol) (Example 1) was added as a solution in anhydrous THF (2 mL) in one portion, the cold bath was removed, and the reaction was stirred at room temperature for 12 hours. THF was evaporated under reduced pressure. Water (2 mL) was added to the residue and the mixture was extracted with three 5 mL portions of EtOAc. The extract was dried over magnesium sulfate. After evaporation, the residue was chromatographed on a silica gel column to provide 86 mg of the title compound as an oil. After the addition the reaction mixture was stirred for 15 to 30 minutes the cold bath was removed the reaction was stirred at room temperature for 12 hours THF was evaporated under reduced pressure Water (2 mL) was added to the residue the mixture was extracted with three 5 mL portions of EtOAc The extract was dried over magnesium sulfate After evaporation the residue was chromatographed on a silica gel column

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

実験手順: A mixture of 2-methylbenzofuran (2.0 g), N-bromosuccinimide (2.7 g) and carbon tetrachloride is heated at reflux overnight. The reaction is filtered and the solvent is removed in vacuo giving 3.8 g (52% monobrominated) of product (62% yield). is heated at reflux overnight The reaction is filtered the solvent is removed in vacuo