ethyl 4-(furan-2-yl)-2,4-dioxobutanoate

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:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To ethyl 4-(2-furyl)-2,4-dioxobutyrate (3.5 g, 16.7 mmol) in 50 mL of glacial acetic acid was added 4-fluoro-3-cyanophenylhydrazine tin chloride (6.3 g, 16.7 mmol). The reaction was stirred at 100° C. for 4 h. The reaction was allowed to cool to room temperature and the acetic acid was removed in vacuo. The residue was diluted with ethyl acetate and the organics were washed with saturated aq NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by recrystallization from hexane/ethyl acetate to afford 2.5 g (46%) of the title compound. LRMS (ES+): 326.1 (M+H)+. to cool to room temperature the acetic acid was removed in vacuo The residue was diluted with ethyl acetate the organics were washed with saturated aq NaHCO3 and brine dried (MgSO4) concentrated The residue was purified by recrystallization from hexane/ethyl acetate

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (5.4 g of 60% dispersion in mineral oil, 136 mmol, mineral oil was removed by washing twice with hexanes) in 100 mL of tetrahydrofuran at ambient temperature was added diethyl oxalate (12.3 mL, 91 mmol). To this mixture was added 2-acetylfuran (5.0 g, 45 mmol) as a solution in 25 mL of tetrahydrofuran. The resulting mixture was stirred at 70° C. for 1 h. The reaction was cooled to room temperature and then 10% HCl was added slowly until the solution was acidic. The tetrahydrofuran was removed in vacuo and the residue was taken up in ethyl acetate. The organics were washed with brine, dried (MgSO4) and concentrated to afford 5.5 g (58%) of the title compound which was used without purification. was removed by washing twice with hexanes) in 100 mL of tetrahydrofuran at ambient temperature The reaction was cooled to room temperature The tetrahydrofuran was removed in vacuo The organics were washed with brine dried (MgSO4) concentrated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (5.4 g of 60% dispersion in mineral oil, 136 mmol, mineral oil was removed by washing twice with hexanes) in 100 mL of tetrahydrofuran at ambient temperature was added diethyl oxalate (12.3 mL, 91 mmol). To this mixture was added 2-acetylfuran (5.0 g, 45 mmol) as a solution in 25 mL of tetrahydrofuran. The resulting mixture was stirred at 70° C. for 1 h. The reaction was cooled to room temperature and then 10% HCl was added slowly until the solution was acidic. The tetrahydrofuran was removed in vacuo and the residue was taken up in ethyl acetate. The organics were washed with brine, dried (MgSO4) and concentrated to afford 5.5 g (58%) of the title compound which was used without purification. was removed by washing twice with hexanes) in 100 mL of tetrahydrofuran at ambient temperature The reaction was cooled to room temperature The tetrahydrofuran was removed in vacuo The organics were washed with brine dried (MgSO4) concentrated

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To ethyl 4-(2-furyl)-2,4-dioxobutyrate (3.5 g, 16.7 mmol) in 50 mL of glacial acetic acid was added 4-fluoro-3-cyanophenylhydrazine tin chloride (6.3 g, 16.7 mmol). The reaction was stirred at 100° C. for 4 h. The reaction was allowed to cool to room temperature and the acetic acid was removed in vacuo. The residue was diluted with ethyl acetate and the organics were washed with saturated aq NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by recrystallization from hexane/ethyl acetate to afford 2.5 g (46%) of the title compound. LRMS (ES+): 326.1 (M+H)+. to cool to room temperature the acetic acid was removed in vacuo The residue was diluted with ethyl acetate the organics were washed with saturated aq NaHCO3 and brine dried (MgSO4) concentrated The residue was purified by recrystallization from hexane/ethyl acetate

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To ethyl 4-(2-furyl)-2,4-dioxobutyrate (3.5 g, 16.7 mmol) in 50 mL of glacial acetic acid was added 4-fluoro-3-cyanophenylhydrazine tin chloride (6.3 g, 16.7 mmol). The reaction was stirred at 100° C. for 4 h. The reaction was allowed to cool to room temperature and the acetic acid was removed in vacuo. The residue was diluted with ethyl acetate and the organics were washed with saturated aq NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by recrystallization from hexane/ethyl acetate to afford 2.5 g (46%) of the title compound. LRMS (ES+): 326.1 (M+H)+. to cool to room temperature the acetic acid was removed in vacuo The residue was diluted with ethyl acetate the organics were washed with saturated aq NaHCO3 and brine dried (MgSO4) concentrated The residue was purified by recrystallization from hexane/ethyl acetate

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (5.4 g of 60% dispersion in mineral oil, 136 mmol, mineral oil was removed by washing twice with hexanes) in 100 mL of tetrahydrofuran at ambient temperature was added diethyl oxalate (12.3 mL, 91 mmol). To this mixture was added 2-acetylfuran (5.0 g, 45 mmol) as a solution in 25 mL of tetrahydrofuran. The resulting mixture was stirred at 70° C. for 1 h. The reaction was cooled to room temperature and then 10% HCl was added slowly until the solution was acidic. The tetrahydrofuran was removed in vacuo and the residue was taken up in ethyl acetate. The organics were washed with brine, dried (MgSO4) and concentrated to afford 5.5 g (58%) of the title compound which was used without purification. was removed by washing twice with hexanes) in 100 mL of tetrahydrofuran at ambient temperature The reaction was cooled to room temperature The tetrahydrofuran was removed in vacuo The organics were washed with brine dried (MgSO4) concentrated

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After a suspension of 10.0 g of 4-furan-2-yl-2,4-dioxo-butyric ethyl ester prepared above and hydroxylamine hydrochloride was stirred at 85° C. for 2 hrs, the solvent was removed under reduced pressure. The concentrate was dissolved in a mixture of methylene chloride and distilled water, followed by separating the organic layer. The organic layer was dried over anhydrous sodium sulfate, filtered through a silica gel layer, and concentrated in vacuo to produce a yield of 8.01 g of 5-furan-2-yl-isoxazole-3-carboxylic acid ethyl ester (Yield 77%). The concentrate was used in the next step without further purification. the solvent was removed under reduced pressure The concentrate was dissolved in a mixture of methylene chloride distilled water by separating the organic layer The organic layer was dried over anhydrous sodium sulfate filtered through a silica gel layer concentrated in vacuo

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

実験手順: 2-acetylfuran was slowly added to a solution of sodium ethoxide (6.81 g) dissolved in absolute ethanol (200 mL) at 0° C. (5.01 mL). This solution was stirred at 0° C. for 2 hrs before oxalic acid diethyl ester (9.30 mL) was slowly added thereto. After stirring for 18 hrs, the reaction was terminated with 1N HCl. The resulting solution was concentrated under reduced pressure to remove the ethanol, followed by extraction with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford 10.0 g of 4-furan-2-yl-2,4-dioxo-butyric acid ethyl ester. This concentrate was used in the next step without further purification. was slowly added the reaction was terminated with 1N HCl The resulting solution was concentrated under reduced pressure to remove the ethanol followed by extraction with methylene chloride The organic layer was dried over anhydrous sodium sulfate filtered concentrated in vacuo

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

実験手順: 2-acetylfuran was slowly added to a solution of sodium ethoxide (6.81 g) dissolved in absolute ethanol (200 mL) at 0° C. (5.01 mL). This solution was stirred at 0° C. for 2 hrs before oxalic acid diethyl ester (9.30 mL) was slowly added thereto. After stirring for 18 hrs, the reaction was terminated with 1N HCl. The resulting solution was concentrated under reduced pressure to remove the ethanol, followed by extraction with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford 10.0 g of 4-furan-2-yl-2,4-dioxo-butyric acid ethyl ester. This concentrate was used in the next step without further purification. was slowly added the reaction was terminated with 1N HCl The resulting solution was concentrated under reduced pressure to remove the ethanol followed by extraction with methylene chloride The organic layer was dried over anhydrous sodium sulfate filtered concentrated in vacuo