1-bromo-3,3,4,4,4-pentafluorobutan-2-one

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

実験手順: A mixture of 2.4 g of 1-bromo-3,3,4,4,4-pentafluorobutan-2-one and 5 ml of DME was added to a mixture of 1.87 g of 2-amino-5-bromo-6-methylpyridine and 10 ml of DME, and the mixture was stirred at room temperature for 3 hours. The precipitated solid was filtered, and washed with 10 ml of DME to obtain 3.95 g of 6-bromo-5-methyl-2-pentafluoroethyl-2,3-dihydroimidazo[1,2-a]pyridin-2-ol hydrobromide. The precipitated solid was filtered washed with 10 ml of DME

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

実験手順: n-Butyl lithium (3.32 ml of a 1.5 molar solution in hexane; 0.00498 mole) in diethylether (5 ml) was cooled and stirred at -78° C. A solution of 2,4-difluorobromobenzene (1.0 g; 0.00519 mole) in ether (8 ml) was added slowly over 15 minutes. The reaction mixture was held for 15 minutes at -78° C. 1-Bromo-3,3,4,4,4-pentafluorobutanone (1.0 g; 0.00415 mole) in 6 ml of ether was then added over 15 minutes at -78° C. The mixture was stirred for 30 minutes at -78° C. Acetic acid (0.7 g) in ether (5 ml) was added followed by water (8 ml), and the mixture was allowed to warm to room temperature. The ether layer was separated and the aqueous layer was washed with 2×15 ml of ether. The combined ether layers were dried over magnesium sulphate and evaporated to give an oil. To this oil were added 1,2,4-triazole (0.86 g; 0.01245 mole); anhydrous potassium carbonate (5.73 g; 0.0415 mole) and anhydrous dimethylformamide (15 ml). The mixture was heated and stirred at 80° C. for 3.5 hours, cooled to room temperature and poured into 150 ml of water. The mixture was then extracted with 3×60 ml methylene chloride, and the combined organic extracts were dried over magnesium sulphate, evaporated and then co-distilled with xylene. The residual brown oil was chromatographed on silica (230-400 mesh) under pressure. Elution with a mixture of ethyl acetate/hexane (60/40 by volume) gave the title compound as a white solid (400 mgs; 28%), melting point 95°-6° C. after crystallization from cyclohexane. The mixture was stirred for 30 minutes at -78° C to warm to room temperature The ether layer was separated the aqueous layer was washed with 2×15 ml of ether The combined ether layers were dried over magnesium sulphate evaporated to give an oil The mixture was heated stirred at 80° C. for 3.5 hours cooled to room temperature The mixture was then extracted with 3×60 ml methylene chloride the combined organic extracts were dried over magnesium sulphate evaporated The residual brown oil was chromatographed on silica (230-400 mesh) under pressure Elution with a mixture of ethyl acetate/hexane (60/40 by volume)

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

実験手順: n-Butyl lithium (3.32 ml of a 1.5 molar solution in hexane; 0.00498 mole) in diethylether (5 ml) was cooled and stirred at -78° C. A solution of 2,4-difluorobromobenzene (1.0 g; 0.00519 mole) in ether (8 ml) was added slowly over 15 minutes. The reaction mixture was held for 15 minutes at -78° C. 1-Bromo-3,3,4,4,4-pentafluorobutanone (1.0 g; 0.00415 mole) in 6 ml of ether was then added over 15 minutes at -78° C. The mixture was stirred for 30 minutes at -78° C. Acetic acid (0.7 g) in ether (5 ml) was added followed by water (8 ml), and the mixture was allowed to warm to room temperature. The ether layer was separated and the aqueous layer was washed with 2×15 ml of ether. The combined ether layers were dried over magnesium sulphate and evaporated to give an oil. To this oil were added 1,2,4-triazole (0.86 g; 0.01245 mole); anhydrous potassium carbonate (5.73 g; 0.0415 mole) and anhydrous dimethylformamide (15 ml). The mixture was heated and stirred at 80° C. for 3.5 hours, cooled to room temperature and poured into 150 ml of water. The mixture was then extracted with 3×60 ml methylene chloride, and the combined organic extracts were dried over magnesium sulphate, evaporated and then co-distilled with xylene. The residual brown oil was chromatographed on silica (230-400 mesh) under pressure. Elution with a mixture of ethyl acetate/hexane (60/40 by volume) gave the title compound as a white solid (400 mgs; 28%), melting point 95°-6° C. after crystallization from cyclohexane. The mixture was stirred for 30 minutes at -78° C to warm to room temperature The ether layer was separated the aqueous layer was washed with 2×15 ml of ether The combined ether layers were dried over magnesium sulphate evaporated to give an oil The mixture was heated stirred at 80° C. for 3.5 hours cooled to room temperature The mixture was then extracted with 3×60 ml methylene chloride the combined organic extracts were dried over magnesium sulphate evaporated The residual brown oil was chromatographed on silica (230-400 mesh) under pressure Elution with a mixture of ethyl acetate/hexane (60/40 by volume)

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

実験手順: n-Butyl lithium (3.32 ml of a 1.5 molar solution in hexane; 0.00498 mole) in diethylether (5 ml) was cooled and stirred at -78° C. A solution of 2,4-difluorobromobenzene (1.0 g; 0.00519 mole) in ether (8 ml) was added slowly over 15 minutes. The reaction mixture was held for 15 minutes at -78° C. 1-Bromo-3,3,4,4,4-pentafluorobutanone (1.0 g; 0.00415 mole) in 6 ml of ether was then added over 15 minutes at -78° C. The mixture was stirred for 30 minutes at -78° C. Acetic acid (0.7 g) in ether (5 ml) was added followed by water (8 ml), and the mixture was allowed to warm to room temperature. The ether layer was separated and the aqueous layer was washed with 2×15 ml of ether. The combined ether layers were dried over magnesium sulphate and evaporated to give an oil. To this oil were added 1,2,4-triazole (0.86 g; 0.01245 mole); anhydrous potassium carbonate (5.73 g; 0.0415 mole) and anhydrous dimethylformamide (15 ml). The mixture was heated and stirred at 80° C. for 3.5 hours, cooled to room temperature and poured into 150 ml of water. The mixture was then extracted with 3×60 ml methylene chloride, and the combined organic extracts were dried over magnesium sulphate, evaporated and then co-distilled with xylene. The residual brown oil was chromatographed on silica (230-400 mesh) under pressure. Elution with a mixture of ethyl acetate/hexane (60/40 by volume) gave the title compound as a white solid (400 mgs; 28%), melting point 95°-6° C. after crystallization from cyclohexane. The mixture was stirred for 30 minutes at -78° C to warm to room temperature The ether layer was separated the aqueous layer was washed with 2×15 ml of ether The combined ether layers were dried over magnesium sulphate evaporated to give an oil The mixture was heated stirred at 80° C. for 3.5 hours cooled to room temperature The mixture was then extracted with 3×60 ml methylene chloride the combined organic extracts were dried over magnesium sulphate evaporated The residual brown oil was chromatographed on silica (230-400 mesh) under pressure Elution with a mixture of ethyl acetate/hexane (60/40 by volume)

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

実験手順: Methyl pentafluoroethyl ketone (3.9 g, 0.02407 mole) (JACS, 78, 2268-70 [1956]) was stirred in concentrated sulphuric acid (10 ml) at room temperature under a dry-ice condenser. Bromine (1.92 g; 0.012035 mole) was added slowly over two hours with vigorous stirring. The mixture was then stirred for one hour at room temperature and then at 50° C. for one hour. The resulting amber solution was distilled at atmospheric pressure, yielding one main fraction of 4.41 g (76%), boiling at 94-97° C. The mass spectrum confirmed the structure, showing parent ions at 240 and 242 m/e corresponding to C4H2BrF5O (2 isotopes of Br). at 50° C. for one hour The resulting amber solution was distilled at atmospheric pressure yielding one main fraction of 4.41 g (76%), boiling at 94-97° C

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

実験手順: 2-(3-Methyl-4-nitrophenyl)-thioacetamide (1.00 g), 1-bromo-3,3,4,4,4-pentafluoro-2-butanone (1.15 g) and potassium carbonate (0.79 g) were stirred in DMF (10 ml) at room temperature for 1 hour. The reaction solution was diluted with ethyl acetate and washed with water and saturated aqueous solution of sodium chloride. After drying the organic layer with magnesium sulfate, the solvent was distilled off under the reduced pressure and the obtained residue was purified by silica gel column chromatography to obtain 2-(3-Methyl-4-nitro-phenyl)-thioacetimidic acid 3,3,4,4,4-pentafluoro-2-oxo-butyl ester (1.30 g). washed with water and saturated aqueous solution of sodium chloride After drying the organic layer with magnesium sulfate the solvent was distilled off under the 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: A mixture of 2.4 g of 1-bromo-3,3,4,4,4-pentafluorobutan-2-one and 5 ml of DME was added to a mixture of 1.87 g of 2-amino-5-bromo-6-methylpyridine and 10 ml of DME, and the mixture was stirred at room temperature for 3 hours. The precipitated solid was filtered, and washed with 10 ml of DME to obtain 3.95 g of 6-bromo-5-methyl-2-pentafluoroethyl-2,3-dihydroimidazo[1,2-a]pyridin-2-ol hydrobromide. The precipitated solid was filtered washed with 10 ml of DME

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

実験手順: A mixture of 2.4 g of 1-bromo-3,3,4,4,4-pentafluorobutan-2-one and 5 ml of DME was added to a mixture of 1.87 g of 2-amino-5-bromo-6-methylpyridine and 10 ml of DME, and the mixture was stirred at room temperature for 3 hours. The precipitated solid was filtered, and washed with 10 ml of DME to obtain 3.95 g of 6-bromo-5-methyl-2-pentafluoroethyl-2,3-dihydroimidazo[1,2-a]pyridin-2-ol hydrobromide. The precipitated solid was filtered washed with 10 ml of DME