tert-butyl 2-bromo-3-oxobutanoate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the compound (1.51 g) obtained in Step 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (1.58 g) in acetonitrile (15 ml) was stirred at 80° C. for 15 min. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2-2:3) to give the title compound (1.29 g). The reaction mixture was concentrated under reduced pressure the residue was partitioned by adding ethyl acetate and water The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtrated concentrated under reduced pressure The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2-2:3)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the compound (2.12 g) obtained in Step 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (2.0 g) in acetonitrile (20 ml) was stirred at 80° C. for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and saturated aqueous sodium carbonate solution. The organic layer was washed successively with saturated aqueous sodium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2) to give the title compound (1.82 g). The reaction mixture was concentrated under reduced pressure the residue was partitioned by adding ethyl acetate and saturated aqueous sodium carbonate solution The organic layer was washed successively with saturated aqueous sodium carbonate solution and saturated brine dried over anhydrous sodium sulfate filtrated concentrated under reduced pressure The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the compound (250 mg) obtained in Example 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (168 mg) in acetonitrile (1.25 ml) was stirred at 80° C. for 20 min. The reaction mixture was concentrated under reduced pressure, and the residue was purified by thin layer chromatography (ethyl acetate:n-hexane=2:3) to give the title compound (268 mg). The reaction mixture was concentrated under reduced pressure the residue was purified by thin layer chromatography (ethyl acetate:n-hexane=2:3)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 7-hydroxy-2-oxo-2H-chromene-3-carbothioic acid amide (221 mg, 1.0 mmol) in anhydrous N,N-dimethylformamide (5 mL) stirred at 0° C., sodium hydride (60% in oil, 44 mg, 1.1 mmol) was added portionwise. During addition a clear solution was formed with moderate effervescence. After 10 min, a solution of 2-bromo-3-oxo butyric acid tert-butyl ester (474 mg, 2.0 mmol) in anhydrous N,N-dimethylformamide (2 mL) was added dropwise and the mixture was stirred at room temperature for 16 h. The reaction was poured into water (20 mL) and extracted with chloroform (3×10 mL). The combined organic extracts were washed with water (3×5 mL), dried over MgSO4 and concentrated. The residue was triturated with diethyl ether, the solid product was collected and washed with diethyl ether. The title compound (224 mg, 0.623 mmol, 62.3%) was obtained as a yellow solid. During addition a clear solution was formed with moderate effervescence the mixture was stirred at room temperature for 16 h extracted with chloroform (3×10 mL) The combined organic extracts were washed with water (3×5 mL) dried over MgSO4 concentrated The residue was triturated with diethyl ether the solid product was collected washed with diethyl ether

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 7-hydroxy-2-oxo-2H-chromene-3-carbothioic acid amide (221 mg, 1.0 mmol) in anhydrous N,N-dimethylformamide (5 mL) stirred at 0° C., sodium hydride (60% in oil, 44 mg, 1.1 mmol) was added portionwise. During addition a clear solution was formed with moderate effervescence. After 10 min, a solution of 2-bromo-3-oxo butyric acid tert-butyl ester (474 mg, 2.0 mmol) in anhydrous N,N-dimethylformamide (2 mL) was added dropwise and the mixture was stirred at room temperature for 16 h. The reaction was poured into water (20 mL) and extracted with chloroform (3×10 mL). The combined organic extracts were washed with water (3×5 mL), dried over MgSO4 and concentrated. The residue was triturated with diethyl ether, the solid product was collected and washed with diethyl ether. The title compound (224 mg, 0.623 mmol, 62.3%) was obtained as a yellow solid. During addition a clear solution was formed with moderate effervescence the mixture was stirred at room temperature for 16 h extracted with chloroform (3×10 mL) The combined organic extracts were washed with water (3×5 mL) dried over MgSO4 concentrated The residue was triturated with diethyl ether the solid product was collected washed with diethyl ether

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

実験手順: To a suspension of sodium acetate (30.76 g, 375 mmol) in DMF (250 mL) was added dropwise tert-Butyl 2-bromo-acetoacetate (59.27 g, 250 mmol). After stirring at ambient temperature for 90 minutes, water (415 mL) was added, followed by extraction with ethyl acetate (3×325 mL). The combined organic layers were washed with water (3×325 mL) and brine (325 mL), dried over Na2SO4 and after filtration, the solvent was removed in vacuo. The resulting oil was purified by distillation (12 mbar, 128°) followed by extraction with ethyl acetate (3×325 mL) The combined organic layers were washed with water (3×325 mL) and brine (325 mL) dried over Na2SO4 after filtration the solvent was removed in vacuo The resulting oil was purified by distillation (12 mbar, 128°)

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

実験手順: To a suspension of sodium acetate (30.76 g, 375 mmol) in DMF (250 mL) was added dropwise tert-Butyl 2-bromo-acetoacetate (59.27 g, 250 mmol). After stirring at ambient temperature for 90 minutes, water (415 mL) was added, followed by extraction with ethyl acetate (3×325 mL). The combined organic layers were washed with water (3×325 mL) and brine (325 mL), dried over Na2SO4 and after filtration, the solvent was removed in vacuo. The resulting oil was purified by distillation (12 mbar, 128°) followed by extraction with ethyl acetate (3×325 mL) The combined organic layers were washed with water (3×325 mL) and brine (325 mL) dried over Na2SO4 after filtration the solvent was removed in vacuo The resulting oil was purified by distillation (12 mbar, 128°)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the compound (1.51 g) obtained in Step 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (1.58 g) in acetonitrile (15 ml) was stirred at 80° C. for 15 min. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2-2:3) to give the title compound (1.29 g). The reaction mixture was concentrated under reduced pressure the residue was partitioned by adding ethyl acetate and water The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtrated concentrated under reduced pressure The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2-2:3)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the compound (2.12 g) obtained in Step 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (2.0 g) in acetonitrile (20 ml) was stirred at 80° C. for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and saturated aqueous sodium carbonate solution. The organic layer was washed successively with saturated aqueous sodium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2) to give the title compound (1.82 g). The reaction mixture was concentrated under reduced pressure the residue was partitioned by adding ethyl acetate and saturated aqueous sodium carbonate solution The organic layer was washed successively with saturated aqueous sodium carbonate solution and saturated brine dried over anhydrous sodium sulfate filtrated concentrated under reduced pressure The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the compound (250 mg) obtained in Example 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (168 mg) in acetonitrile (1.25 ml) was stirred at 80° C. for 20 min. The reaction mixture was concentrated under reduced pressure, and the residue was purified by thin layer chromatography (ethyl acetate:n-hexane=2:3) to give the title compound (268 mg). The reaction mixture was concentrated under reduced pressure the residue was purified by thin layer chromatography (ethyl acetate:n-hexane=2:3)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 7-hydroxy-2-oxo-2H-chromene-3-carbothioic acid amide (221 mg, 1.0 mmol) in anhydrous N,N-dimethylformamide (5 mL) stirred at 0° C., sodium hydride (60% in oil, 44 mg, 1.1 mmol) was added portionwise. During addition a clear solution was formed with moderate effervescence. After 10 min, a solution of 2-bromo-3-oxo butyric acid tert-butyl ester (474 mg, 2.0 mmol) in anhydrous N,N-dimethylformamide (2 mL) was added dropwise and the mixture was stirred at room temperature for 16 h. The reaction was poured into water (20 mL) and extracted with chloroform (3×10 mL). The combined organic extracts were washed with water (3×5 mL), dried over MgSO4 and concentrated. The residue was triturated with diethyl ether, the solid product was collected and washed with diethyl ether. The title compound (224 mg, 0.623 mmol, 62.3%) was obtained as a yellow solid. During addition a clear solution was formed with moderate effervescence the mixture was stirred at room temperature for 16 h extracted with chloroform (3×10 mL) The combined organic extracts were washed with water (3×5 mL) dried over MgSO4 concentrated The residue was triturated with diethyl ether the solid product was collected washed with diethyl ether

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

実験手順: To a suspension of sodium acetate (30.76 g, 375 mmol) in DMF (250 mL) was added dropwise tert-Butyl 2-bromo-acetoacetate (59.27 g, 250 mmol). After stirring at ambient temperature for 90 minutes, water (415 mL) was added, followed by extraction with ethyl acetate (3×325 mL). The combined organic layers were washed with water (3×325 mL) and brine (325 mL), dried over Na2SO4 and after filtration, the solvent was removed in vacuo. The resulting oil was purified by distillation (12 mbar, 128°) followed by extraction with ethyl acetate (3×325 mL) The combined organic layers were washed with water (3×325 mL) and brine (325 mL) dried over Na2SO4 after filtration the solvent was removed in vacuo The resulting oil was purified by distillation (12 mbar, 128°)