ethyl 6-methyl-2,4-dioxoheptanoate

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Potassium acetate (49.1 g, 0.500 mol) was added with stirring to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (44.4 g, 0.200 mol), prepared as described in Part A of Examples 1-4, in acetic acid (280 mL). The solution was cooled to 10° C., and benzylhydrazine dihydrochloride (39.0 g, 0.200 mol) was added in portions over a period of ten minutes while the reaction temperature was maintained between 10° C. and 13.5° C. The reaction was stirred for 90 minutes at between 6° C. and 13.6° C., allowed to warm to ambient temperature, stirred overnight, and concentrated under reduced pressure. The residue was partitioned between 2 M aqueous sodium carbonate (900 mL) and tert-butyl methyl ether (600 mL). The aqueous layer was extracted with tert-butyl methyl ether (2×300 mL), and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 56.6 g of ethyl 1-benzyl-5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as an oil orange. The product contained 10 mol % of ethyl 2-benzyl-5-(2-methylpropyl)-2H-pyrazole-3-carboxylate. prepared was maintained between 10° C. and 13.5° C to warm to ambient temperature stirred overnight concentrated under reduced pressure The residue was partitioned between 2 M aqueous sodium carbonate (900 mL) and tert-butyl methyl ether (600 mL) The aqueous layer was extracted with tert-butyl methyl ether (2×300 mL) the combined organic fractions were dried over magnesium sulfate filtered concentrated under reduced pressure

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

実験手順: Anhydrous hydrazine (3.58 g, 112 mmol) was added dropwise over a period of 30 minutes to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (24.8 g, 112 mmol) in acetic acid (160 mL). The reaction was stirred overnight at ambient temperature, and then the solvent was removed under reduced pressure. The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added to adjust the mixture to pH 8. The aqueous layer was extracted twice with diethyl ether; the combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes) to provide 21.0 g of ethyl 5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as a solid. the solvent was removed under reduced pressure The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added The aqueous layer was extracted twice with diethyl ether the combined organic fractions were washed with brine dried over magnesium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes)

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

実験手順: Anhydrous hydrazine (3.58 g, 112 mmol) was added dropwise over a period of 30 minutes to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (24.8 g, 112 mmol) in acetic acid (160 mL). The reaction was stirred overnight at ambient temperature, and then the solvent was removed under reduced pressure. The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added to adjust the mixture to pH 8. The aqueous layer was extracted twice with diethyl ether; the combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes) to provide 21.0 g of ethyl 5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as a solid. the solvent was removed under reduced pressure The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added The aqueous layer was extracted twice with diethyl ether the combined organic fractions were washed with brine dried over magnesium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes)

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

実験手順: Anhydrous hydrazine (3.58 g, 112 mmol) was added dropwise over a period of 30 minutes to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (24.8 g, 112 mmol) in acetic acid (160 mL). The reaction was stirred overnight at ambient temperature, and then the solvent was removed under reduced pressure. The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added to adjust the mixture to pH 8. The aqueous layer was extracted twice with diethyl ether; the combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes) to provide 21.0 g of ethyl 5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as a solid. the solvent was removed under reduced pressure The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added The aqueous layer was extracted twice with diethyl ether the combined organic fractions were washed with brine dried over magnesium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1H-Benzoimidazol-5-ylamine (1 mmol) and 8-Hydroxy-quinoline-2-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 6-Methyl-2,4-dioxo-heptanoic acid ethyl ester (1 mmol) was added. The reaction was heated to 50° C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods. After evaporation of the solvent the residue was purified with chromatographic methods

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Potassium acetate (49.1 g, 0.500 mol) was added with stirring to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (44.4 g, 0.200 mol), prepared as described in Part A of Examples 1-4, in acetic acid (280 mL). The solution was cooled to 10° C., and benzylhydrazine dihydrochloride (39.0 g, 0.200 mol) was added in portions over a period often minutes while the reaction temperature was maintained between 10° C. and 13.5° C. The reaction was stirred for 90 minutes at between 6° C. and 13.6° C., allowed to warm to ambient temperature, stirred overnight, and concentrated under reduced pressure. The residue was partitioned between 2 M aqueous sodium carbonate (900 mL) and tert-butyl methyl ether (600 mL). The aqueous layer was extracted with tert-butyl methyl ether (2×300 mL), and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 56.6 g of ethyl 1-benzyl-5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as an oil orange. The product contained 10 mol % of ethyl 2-benzyl-5-(2-methylpropyl)-2H-pyrazole-3-carboxylate. prepared was maintained between 10° C. and 13.5° C to warm to ambient temperature stirred overnight concentrated under reduced pressure The residue was partitioned between 2 M aqueous sodium carbonate (900 mL) and tert-butyl methyl ether (600 mL) The aqueous layer was extracted with tert-butyl methyl ether (2×300 mL) the combined organic fractions were dried over magnesium sulfate filtered concentrated under reduced pressure

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

実験手順: Anhydrous hydrazine (3.58 g, 112 mmol) was added dropwise over a period of 30 minutes to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (24.8 g, 112 mmol) in acetic acid (160 mL). The reaction was stirred overnight at ambient temperature, and then the solvent was removed under reduced pressure. The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added to adjust the mixture to pH 8. The aqueous layer was extracted twice with diethyl ether; the combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes) to provide 21.0 g of ethyl 5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as a solid. the solvent was removed under reduced pressure The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added The aqueous layer was extracted twice with diethyl ether the combined organic fractions were washed with brine dried over magnesium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes)

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Potassium acetate (49.1 g, 0.500 mol) was added with stirring to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (44.4 g, 0.200 mol), prepared as described in Part A of Examples 1-4, in acetic acid (280 mL). The solution was cooled to 10° C., and benzylhydrazine dihydrochloride (39.0 g, 0.200 mol) was added in portions over a period of ten minutes while the reaction temperature was maintained between 10° C. and 13.5° C. The reaction was stirred for 90 minutes at between 6° C. and 13.6° C., allowed to warm to ambient temperature, stirred overnight, and concentrated under reduced pressure. The residue was partitioned between 2 M aqueous sodium carbonate (900 mL) and tert-butyl methyl ether (600 mL). The aqueous layer was extracted with tert-butyl methyl ether (2×300 mL), and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 56.6 g of ethyl 1-benzyl-5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as an oil orange. The product contained 10 mol % of ethyl 2-benzyl-5-(2-methylpropyl)-2H-pyrazole-3-carboxylate. prepared was maintained between 10° C. and 13.5° C to warm to ambient temperature stirred overnight concentrated under reduced pressure The residue was partitioned between 2 M aqueous sodium carbonate (900 mL) and tert-butyl methyl ether (600 mL) The aqueous layer was extracted with tert-butyl methyl ether (2×300 mL) the combined organic fractions were dried over magnesium sulfate filtered concentrated under reduced pressure

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

実験手順: Anhydrous hydrazine (3.58 g, 112 mmol) was added dropwise over a period of 30 minutes to a solution of ethyl 6-methyl-2,4-dioxoheptanoate, sodium salt (24.8 g, 112 mmol) in acetic acid (160 mL). The reaction was stirred overnight at ambient temperature, and then the solvent was removed under reduced pressure. The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added to adjust the mixture to pH 8. The aqueous layer was extracted twice with diethyl ether; the combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes) to provide 21.0 g of ethyl 5-(2-methylpropyl)-1H-pyrazole-3-carboxylate as a solid. the solvent was removed under reduced pressure The residue was dissolved in a mixture of diethyl ether and water, and solid sodium bicarbonate and sodium carbonate were added The aqueous layer was extracted twice with diethyl ether the combined organic fractions were washed with brine dried over magnesium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a HORIZON HPFC system (FLASH 65I cartridge, eluting with 50:50 ethyl acetate/hexanes)