tert-butyl N-[(2S)-3-oxobutan-2-yl]carbamate

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl magnesium bromide (3.0M solution in diethyl ether, 4.3 ml, 12.9 mmol) was added to a stirred solution of tert-butyl (1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethylcarbamate (Tetrahedron: Asymmetry 1996, 7, 985) (1 g, 4.3 mmol) in anhydrous tetrahydrofuran (20 ml) at −60° C. under a nitrogen atmosphere. The mixture was allowed to warm to 0° C. and to then room temperature and was stirred at room temperature for 1 hour. Aqueous saturated ammonium chloride was added and aqueous phase was extracted with diethyl ether (2×76 ml). The combined organic extracts were then washed with saturated aqueous ammonium chloride solution and brine. The organic phase was then dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of dichloromethane:methanol (99:1 to 98:2), to afford the title compound as a colorless solid, 412 mg, 51% yield. aqueous phase was extracted with diethyl ether (2×76 ml) The combined organic extracts were then washed with saturated aqueous ammonium chloride solution and brine The organic phase was then dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (99:1 to 98:2)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl magnesium bromide (3.0M solution in diethyl ether, 4.3 ml, 12.9 mmol) was added to a stirred solution of tert-butyl (1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethylcarbamate (Tetrahedron: Asymmetry 1996, 7, 985) (1 g, 4.3 mmol) in anhydrous tetrahydrofuran (20 ml) at −60° C. under a nitrogen atmosphere. The mixture was allowed to warm to 0° C. and to then room temperature and was stirred at room temperature for 1 hour. Aqueous saturated ammonium chloride was added and aqueous phase was extracted with diethyl ether (2×76 ml). The combined organic extracts were then washed with saturated aqueous ammonium chloride solution and brine. The organic phase was then dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of dichloromethane:methanol (99:1 to 98:2), to afford the title compound as a colorless solid, 412 mg, 51% yield. aqueous phase was extracted with diethyl ether (2×76 ml) The combined organic extracts were then washed with saturated aqueous ammonium chloride solution and brine The organic phase was then dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (99:1 to 98:2)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (3.44 g) in tetrahydrofuran (50 mL) was ice-cooled under a nitrogen atmosphere and 1.6 mol/L n-butyllithium-hexane solution (20.8 mL) was added. The mixture was stirred at the same temperature for 20 min, and the reaction solution was cooled with dry ice/acetone. Ethyl acetate (3.28 mL) was added to the reaction solution, and the mixture was stirred at the same temperature for 30 min. A solution of tert-butyl [(1S)-1-methyl-2-oxopropyl]carbamate (4.48 g) in tetrahydrofuran (10 mL) was added. The mixture was stirred at the same temperature for 5 hr, saturated aqueous ammonium chloride solution (100 mL) was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→30%), the obtained oil was dissolved in 4 mol/L hydrogen chloride-ethyl acetate solution (50 mL), and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under reduced pressure, the residue was dissolved in tetrahydrofuran (150 mL), and diisopropylethylamine (11.5 mL) was added. The reaction solution was refluxed under heating for 4 hr, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate=0→10%), and the obtained solid was recrystallized from isopropanol/hexane to give the title compound as colorless crystals (yield: 1.51 g, 55%). cooled under a nitrogen atmosphere 1.6 mol/L n-butyllithium-hexane solution (20.8 mL) was added the mixture was stirred at the same temperature for 30 min The mixture was stirred at the same temperature for 5 hr the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→30%) the obtained oil was dissolved in 4 mol/L hydrogen chloride-ethyl acetate solution (50 mL) the mixture was stirred at room temperature for 2 hr The reaction solution was concentrated under reduced pressure the residue was dissolved in tetrahydrofuran (150 mL) diisopropylethylamine (11.5 mL) was added The reaction solution was refluxed under heating for 4 hr concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate=0→10%) the obtained solid was recrystallized from isopropanol/hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl{(1S)-1-[methoxy(methyl)carbamoyl]ethyl}carbamate (5.26 g) in tetrahydrofuran (300 mL) was cooled with dry ice/acetone under a nitrogen atmosphere, and 1.6 mol/L-methyllithium/diethyl ether solution (38.8 mL) was added. After stirring at the same temperature for 1.5 hr, saturated aqueous ammonium chloride solution (100 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentration under reduced pressure to give the title compound as a colorless oil (yield: 4.48 g). the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate, and concentration under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of diisopropylamine (3.44 g) in tetrahydrofuran (50 mL) was ice-cooled under a nitrogen atmosphere and 1.6 mol/L n-butyllithium-hexane solution (20.8 mL) was added. The mixture was stirred at the same temperature for 20 min, and the reaction solution was cooled with dry ice/acetone. Ethyl acetate (3.28 mL) was added to the reaction solution, and the mixture was stirred at the same temperature for 30 min. A solution of tert-butyl [(1S)-1-methyl-2-oxopropyl]carbamate (4.48 g) in tetrahydrofuran (10 mL) was added. The mixture was stirred at the same temperature for 5 hr, saturated aqueous ammonium chloride solution (100 mL) was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→30%), the obtained oil was dissolved in 4 mol/L hydrogen chloride-ethyl acetate solution (50 mL), and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under reduced pressure, the residue was dissolved in tetrahydrofuran (150 mL), and diisopropylethylamine (11.5 mL) was added. The reaction solution was refluxed under heating for 4 hr, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate=0→10%), and the obtained solid was recrystallized from isopropanol/hexane to give the title compound as colorless crystals (yield: 1.51 g, 55%). cooled under a nitrogen atmosphere 1.6 mol/L n-butyllithium-hexane solution (20.8 mL) was added the mixture was stirred at the same temperature for 30 min The mixture was stirred at the same temperature for 5 hr the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→30%) the obtained oil was dissolved in 4 mol/L hydrogen chloride-ethyl acetate solution (50 mL) the mixture was stirred at room temperature for 2 hr The reaction solution was concentrated under reduced pressure the residue was dissolved in tetrahydrofuran (150 mL) diisopropylethylamine (11.5 mL) was added The reaction solution was refluxed under heating for 4 hr concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate=0→10%) the obtained solid was recrystallized from isopropanol/hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of tert-butyl{(1S)-1-[methoxy(methyl)carbamoyl]ethyl}carbamate (5.26 g) in tetrahydrofuran (300 mL) was cooled with dry ice/acetone under a nitrogen atmosphere, and 1.6 mol/L-methyllithium/diethyl ether solution (38.8 mL) was added. After stirring at the same temperature for 1.5 hr, saturated aqueous ammonium chloride solution (100 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentration under reduced pressure to give the title compound as a colorless oil (yield: 4.48 g). the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate, and concentration under reduced pressure

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl magnesium bromide (3.0M solution in diethyl ether, 4.3 ml, 12.9 mmol) was added to a stirred solution of tert-butyl (1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethylcarbamate (Tetrahedron: Asymmetry 1996, 7, 985) (1 g, 4.3 mmol) in anhydrous tetrahydrofuran (20 ml) at −60° C. under a nitrogen atmosphere. The mixture was allowed to warm to 0° C. and to then room temperature and was stirred at room temperature for 1 hour. Aqueous saturated ammonium chloride was added and aqueous phase was extracted with diethyl ether (2×76 ml). The combined organic extracts were then washed with saturated aqueous ammonium chloride solution and brine. The organic phase was then dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of dichloromethane:methanol (99:1 to 98:2), to afford the title compound as a colorless solid, 412 mg, 51% yield. aqueous phase was extracted with diethyl ether (2×76 ml) The combined organic extracts were then washed with saturated aqueous ammonium chloride solution and brine The organic phase was then dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (99:1 to 98:2)