2-bromo-2-methyl-1-phenylpropan-1-one

反応条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 45.4 g (0.2 mol) of α-bromoisobutyrophenone and 1 g of potassium iodide are added to 14 g (0.2 mol) of triazole and 27 g (0.2 mol) of potassium carbonate in 100 ml of acetonitrile at 75° C. When the addition has ended, the mixture is stirred at 75° C. for a further 8 hours, filtered and rinsed with acetonitrile. The filtrate is concentrated, the residue is taken up in chloroform and the mixture is washed twice with water, dried over sodium sulphate and freed from the solvent in vacuo. The residue is recrystallized from ethyl acetate/petroleum ether. 12.1 g (28% of theory) of α-(1,2,4-triazol-1-yl)-isobutyrophenone of melting point 134° C. to 135° C. are obtained. When the addition filtered rinsed with acetonitrile The filtrate is concentrated the mixture is washed twice with water dried over sodium sulphate The residue is recrystallized from ethyl acetate/petroleum ether

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

実験手順: In a dried 3 neck flask fitted with magnetic stirrer and condensor was placed metal magnesium (12 mmol) and ether (1.8 mL) Neat bromoethane (2.5 mmol) was added via syringe and the reaction was started immediately. A solution of bromoethane (10.5 mmol) in toluene (30 mL) was added to the solution slowly. After completion of the addition, the solution was stirred at room temperature for 30 min under nitrogen before adding neat diethylamine (24 mmol). The solution was further stirred at room temperature for 15 min. The solution was cooled to 0° C. and a mixture of 1-(pyridin-2-yl)ethanone (XVIII) (12 mmol) and 2-bromoisobutyrophenone (XVII) (13 mmol) was added to the solution. The solution was further stirred for 3 h at 0° C. under nitrogen. Aqueous 5% H2SO4 (20 mL) was added to the solution and the solution was warmed to room temperature. The organic layer was separated, dried over MgSO4 and filtered. The organic layer was then treated with Et3N (10 mmol) and allowed to stir overnight at room temperature. The solution was then washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient to give 2,2-dimethyl-1-phenyl-4-(pyridin-2-yl)butane-1,4-dione 9 as a colorless viscous oil (11% yield). 1H NMR (CDCl3, 400 MHz): δ ppm 1.47 (s, 6H), 3.80 (s, 2H), 7.34-7.50 (m, 4H), 7.65-7.75 (m, 2H), 7.80 (m, 1H), 7.94 (m, 1H), 8.67 (m, 1H); ESIMS found C17H17NO2 m/z 268 (M+H). In a dried 3 neck flask fitted with magnetic stirrer was added via syringe After completion of the addition The solution was further stirred at room temperature for 15 min The solution was cooled to 0° C. was added to the solution The solution was further stirred for 3 h at 0° C. under nitrogen the solution was warmed to room temperature The organic layer was separated dried over MgSO4 filtered to stir overnight at room temperature The solution was then washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient

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

実験手順: In a dried 3 neck flask fitted with magnetic stirrer and condensor was placed metal magnesium (12 mmol) and ether (1.8 mL). Neat bromoethane (2.5 mmol) was added via syringe and the reaction was started immediately. A solution of bromoethane (10.5 mmol) in toluene (30 mL) was added to the solution slowly. After completion of the addition, the solution was stirred at room temperature for 30 min under nitrogen before adding neat diethylamine (24 mmol). The solution was further stirred at room temperature for 15 min. The solution was cooled to 0° C. and a mixture of 1-(pyridin-2-yl)ethanone (XVIII) (12 mmol) and 2-bromoisobutyrophenone (XVII) (13 mmol) was added to the solution. The solution was further stirred for 3 h at 0° C. under nitrogen. Aqueous 5% H2SO4 (20 mL) was added to the solution and the solution was warmed to room temperatue. The organic layer was separated, dried over MgSO4 and filtered. The organic layer was then treated with Et3N (10 mmol) and allowed to stir overnight at room temperature. The solution was then washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient to give 2,2-dimethyl-1-phenyl-4-(pyridin-2-yl)butane-1,4-dione 9 as a colorless viscous oil (11% yield). 1H NMR (CDCl3, 400 MHz): δ ppm 1.47 (s, 6H), 3.80 (s, 2H), 7.34-7.50 (m, 4H), 7.65-7.75 (m, 2H), 7.80 (m, 1H), 7.94 (m, 1H), 8.67 (m, 1H); ESIMS found C17H17NO2 m/z 268 (M+H). In a dried 3 neck flask fitted with magnetic stirrer After completion of the addition The solution was further stirred at room temperature for 15 min The solution was cooled to 0° C. was added to the solution The solution was further stirred for 3 h at 0° C. under nitrogen the solution was warmed to room temperatue The organic layer was separated dried over MgSO4 filtered to stir overnight at room temperature The solution was then washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient

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

実験手順: In a dried 3 neck flask fitted with magnetic stirrer and condensor was placed metal magnesium (12 mmol) and ether (1.8 mL). Neat bromoethane (2.5 mmol) was added via syringe and the reaction was started immediately. A solution of bromoethane (10.5 mmol) in toluene (30 mL) was added to the solution slowly. After completion of the addition, the solution was stirred at room temperature for 30 min under nitrogen before adding neat diethylamine (24 mmol). The solution was further stirred at room temperature for 15 min. The solution was cooled to 0° C. and a mixture of 1-(pyridin-2-yl)ethanone (XVIII) (12 mmol) and 2-bromoisobutyrophenone (XVII) (13 mmol) was added to the solution. The solution was further stirred for 3 h at 0° C. under nitrogen. Aqueous 5% H2SO4 (20 mL) was added to the solution and the solution was warmed to room temperatue. The organic layer was separated, dried over MgSO4 and filtered. The organic layer was then treated with Et3N (10 mmol) and allowed to stir overnight at room temperature. The solution was then washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient to give 2,2-dimethyl-1-phenyl-4-(pyridin-2-yl)butane-1,4-dione 9 as a colorless viscous oil (11% yield). 1H NMR (CDCl3, 400 MHz): δ ppm 1.47 (s, 6H), 3.80 (s, 2H), 7.34-7.50 (m, 4H), 7.65-7.75 (m, 2H), 7.80 (m, 1H), 7.94 (m, 1H), 8.67 (m, 1H); ESIMS found C17H17NO2 m/z 268 (M+H). In a dried 3 neck flask fitted with magnetic stirrer After completion of the addition The solution was further stirred at room temperature for 15 min The solution was cooled to 0° C. was added to the solution The solution was further stirred for 3 h at 0° C. under nitrogen the solution was warmed to room temperatue The organic layer was separated dried over MgSO4 filtered to stir overnight at room temperature The solution was then washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient

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

実験手順: A solution of 4.6 g (0.02 mol) of α-bromoisobutyrophenone and 1.8 g (0.022 mol) of 1-methylimidazole in 30 ml of diethyl ether was stirred at room temperature for approximately 48 hours. The solvent was decanted and the resulting oil was slurried in ethyl acetate. The solvent was again decanted and the residue was dissolved in acetonitrile prior to adding a small portion of ethyl acetate. A white precipitate was collected by filtration and recrystallized from methanol/ethyl acetate to afford 3.88 g of 1-methyl-3-(1,1-dimethyl-2-phenyl-2-oxoethyl)-1H-imidazolium bromide as glittering white flakes. (63% yield) mp=137°-140° C. The solvent was decanted The solvent was again decanted the residue was dissolved in acetonitrile to adding a small portion of ethyl acetate A white precipitate was collected by filtration recrystallized from methanol/ethyl acetate

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

実験手順: A solution of 4.6 g (0.02 mol) of α-bromoisobutyrophenone and 1.8 g (0.022 mol) of 1-methylimidazole in 30 ml of diethyl ether was stirred at room temperature for approximately 48 hours. The solvent was decanted and the resulting oil was slurried in ethyl acetate. The solvent was again decanted and the residue was dissolved in acetonitrile prior to adding a small portion of ethyl acetate. A white precipitate was collected by filtration and recrystallized from methanol/ethyl acetate to afford 3.88 g of 1-methyl-3-(1,1-dimethyl-2-phenyl-2-oxoethyl)-1H-imidazolium bromide as glittering white flakes. (63% yield) mp=137°-140° C. The solvent was decanted The solvent was again decanted the residue was dissolved in acetonitrile to adding a small portion of ethyl acetate A white precipitate was collected by filtration recrystallized from methanol/ethyl acetate

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

実験手順: In a dried 3 neck flask fitted with magnetic stirrer and condensor was placed metal magnesium (12 mmol) and ether (1.8 mL) Neat bromoethane (2.5 mmol) was added via syringe and the reaction was started immediately. A solution of bromoethane (10.5 mmol) in toluene (30 mL) was added to the solution slowly. After completion of the addition, the solution was stirred at room temperature for 30 min under nitrogen before adding neat diethylamine (24 mmol). The solution was further stirred at room temperature for 15 min. The solution was cooled to 0° C. and a mixture of 1-(pyridin-2-yl)ethanone (XVIII) (12 mmol) and 2-bromoisobutyrophenone (XVII) (13 mmol) was added to the solution. The solution was further stirred for 3 h at 0° C. under nitrogen. Aqueous 5% H2SO4 (20 mL) was added to the solution and the solution was warmed to room temperature. The organic layer was separated, dried over MgSO4 and filtered. The organic layer was then treated with Et3N (10 mmol) and allowed to stir overnight at room temperature. The solution was then washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient to give 2,2-dimethyl-1-phenyl-4-(pyridin-2-yl)butane-1,4-dione 9 as a colorless viscous oil (11% yield). 1H NMR (CDCl3, 400 MHz): δ ppm 1.47 (s, 6H), 3.80 (s, 2H), 7.34-7.50 (m, 4H), 7.65-7.75 (m, 2H), 7.80 (m, 1H), 7.94 (m, 1H), 8.67 (m, 1H); ESIMS found C17H17NO2 m/z 268 (M+H). In a dried 3 neck flask fitted with magnetic stirrer was added via syringe After completion of the addition The solution was further stirred at room temperature for 15 min The solution was cooled to 0° C. was added to the solution The solution was further stirred for 3 h at 0° C. under nitrogen the solution was warmed to room temperature The organic layer was separated dried over MgSO4 filtered to stir overnight at room temperature The solution was then washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient

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

実験手順: A solution of 4.6 g (0.02 mol) of α-bromoisobutyrophenone and 1.8 g (0.022 mol) of 1-methylimidazole in 30 ml of diethyl ether was stirred at room temperature for approximately 48 hours. The solvent was decanted and the resulting oil was slurried in ethyl acetate. The solvent was again decanted and the residue was dissolved in acetonitrile prior to adding a small portion of ethyl acetate. A white precipitate was collected by filtration and recrystallized from methanol/ethyl acetate to afford 3.88 g of 1-methyl-3-(1,1-dimethyl-2-phenyl-2-oxoethyl)-1H-imidazolium bromide as glittering white flakes. (63% yield) mp=137°-140° C. The solvent was decanted The solvent was again decanted the residue was dissolved in acetonitrile to adding a small portion of ethyl acetate A white precipitate was collected by filtration recrystallized from methanol/ethyl acetate

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

実験手順: To a suspension of 2-amino-5-nitrophenol (3.00 g) in N,N-dimethyl-formamide (30 mL) was added potassium fluoride (3.40 g), and the mixture was stirred at room temperature for 15 minutes, and thereto was added 2-bromo-2-methylpropiophenone (4.42 g). The mixture was stirred at room temperature for 0.5 hour, at 60° C. for 20 hours and at 80° C. for 3 days. After cooling, to the reaction mixture was added cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over sodium sulfate and concentrated in vacuo. The resultant residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=10/1) to give 2,2-dimethyl-7-nitro-3-phenyl-2H-1,4-benzoxazine (3.65 g) as a pale yellow powder. The mixture was stirred at room temperature for 0.5 hour, at 60° C. for 20 hours and at 80° C. for 3 days After cooling, to the reaction mixture the mixture was extracted with ethyl acetate The organic layer was washed successively with water and brine dried over sodium sulfate concentrated in vacuo The resultant residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=10/1)

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

実験手順: In a dried 3 neck flask fitted with magnetic stirrer and condensor was placed metal magnesium (12 mmol) and ether (1.8 mL). Neat bromoethane (2.5 mmol) was added via syringe and the reaction was started immediately. A solution of bromoethane (10.5 mmol) in toluene (30 mL) was added to the solution slowly. After completion of the addition, the solution was stirred at room temperature for 30 min under nitrogen before adding neat diethylamine (24 mmol). The solution was further stirred at room temperature for 15 min. The solution was cooled to 0° C. and a mixture of 1-(pyridin-2-yl)ethanone (XVIII) (12 mmol) and 2-bromoisobutyrophenone (XVII) (13 mmol) was added to the solution. The solution was further stirred for 3 h at 0° C. under nitrogen. Aqueous 5% H2SO4 (20 mL) was added to the solution and the solution was warmed to room temperatue. The organic layer was separated, dried over MgSO4 and filtered. The organic layer was then treated with Et3N (10 mmol) and allowed to stir overnight at room temperature. The solution was then washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient to give 2,2-dimethyl-1-phenyl-4-(pyridin-2-yl)butane-1,4-dione 9 as a colorless viscous oil (11% yield). 1H NMR (CDCl3, 400 MHz): δ ppm 1.47 (s, 6H), 3.80 (s, 2H), 7.34-7.50 (m, 4H), 7.65-7.75 (m, 2H), 7.80 (m, 1H), 7.94 (m, 1H), 8.67 (m, 1H); ESIMS found C17H17NO2 m/z 268 (M+H). In a dried 3 neck flask fitted with magnetic stirrer After completion of the addition The solution was further stirred at room temperature for 15 min The solution was cooled to 0° C. was added to the solution The solution was further stirred for 3 h at 0° C. under nitrogen the solution was warmed to room temperatue The organic layer was separated dried over MgSO4 filtered to stir overnight at room temperature The solution was then washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient

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

実験手順: To a suspension of 2-amino-5-nitrophenol (3.00 g) in N,N-dimethylformamide (30 mL) was added potassium fluoride (3.40 g), and the mixture was stirred at room temperature for 15 minutes, and thereto was added 2-bromo-2-methylpropiophenone (4.42 g). The mixture was stirred at room temperature for 0.5 hour, at 60° C. for 20 hours and at 80° C. for 3 days. After cooling, to the reaction mixture was added cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over sodium sulfate and concentrated in vacuo. The resultant residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=10/1) to give 2,2-dimethyl-7-nitro-3-phenyl-2H-1,4-benzoxazine (3.65 g) as a pale yellow powder. The mixture was stirred at room temperature for 0.5 hour, at 60° C. for 20 hours and at 80° C. for 3 days After cooling, to the reaction mixture the mixture was extracted with ethyl acetate The organic layer was washed successively with water and brine dried over sodium sulfate concentrated in vacuo The resultant residue was purified by column chromatography on silica gel (solvent; n-hexane/ethyl acetate=10/1)

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

実験手順: In a dried 3 neck flask fitted with magnetic stirrer and condenser was placed metal magnesium (12 mmol) and ether (1.8 mL). Neat bromoethane (2.5 mmol) was added via syringe and the reaction was started immediately. A solution of bromoethane (10.5 mmol) in toluene (30 mL) was added to the solution slowly. After completion of the addition, the solution was stirred at room temperature for 30 min under nitrogen before adding neat diethylamine (24 mmol). The solution was further stirred at room temperature for 15 min. The solution was cooled to 0° C. and a mixture of 1-(pyridin-2-yl)ethanone (XVIII) (12 mmol) and 2-bromoisobutyrophenone (XVII) (13 mmol) was added to the solution. The solution was further stirred for 3 h at 0° C. under nitrogen. Aqueous 5% H2SO4 (20 mL) was added to the solution and the solution was warmed to room temperature. The organic layer was separated, dried over MgSO4 and filtered. The organic layer was then treated with Et3N (10 mmol) and allowed to stir overnight at room temperature. The solution was then washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient to give 2,2-dimethyl-1-phenyl-4-(pyridin-2-yl)butane-1,4-dione 9 as a colorless viscous oil (11% yield). 1H NMR (CDCl3, 400 MHz): δ ppm 1.47 (s, 6H), 3.80 (s, 2H), 7.34-7.50 (m, 4H), 7.65-7.75 (m, 2H), 7.80 (m, 1H), 7.94 (m, 1H), 8.67 (m, 1H); ESIMS found C17H17NO2 m/z 268 (M+H). In a dried 3 neck flask fitted with magnetic stirrer and condenser After completion of the addition The solution was further stirred at room temperature for 15 min The solution was cooled to 0° C. was added to the solution The solution was further stirred for 3 h at 0° C. under nitrogen the solution was warmed to room temperature The organic layer was separated dried over MgSO4 filtered to stir overnight at room temperature The solution was then washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography eluting with 1-5% EtOAc in hexane gradient