Methyl 3-((tert-butoxycarbonyl)(methyl)amino)propanoate

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

実験手順: To a solution of N-t-butoxycarbonyl-N-methyl-β-alanine methyl ester (3.911 g) in methanol (20 ml) and water (20 ml) was added sodium borohydride (6.81 g) portionwise at 4° C. and the mixture was stirred at room temperature for 3 hours. The solution was concentrated in vacuo, and the residue was portioned between ethyl acetate (100 ml) and 0.5 N hydrochloric acid (100 ml). The separated organic layer was washed with 0.5 N hydrochloric acid (100 ml), water (100 ml), aqueous sodium bicarbonate (100 ml), water (100 ml) and brine (100 ml) successively, and dried over magnesium sulfate. Evaporation of the solvent gave 3-(N-t-butoxycarbonyl-N-methylamino)propanol (2.48 g) as an oil. The solution was concentrated in vacuo The separated organic layer was washed with 0.5 N hydrochloric acid (100 ml), water (100 ml), aqueous sodium bicarbonate (100 ml), water (100 ml) and brine (100 ml) successively dried over magnesium sulfate Evaporation of the solvent

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

実験手順: To a solution of N-t-butoxycarbonyl-N-methyl-β-alanine methyl ester (3.911 g) in methanol (20 ml) and water (20 ml) was added sodium borohydride (6.81 g) portionwise at 4° C. and the mixture was stirred at room temperature for 3 hours. The solution was concentrated in vacuo, and the residue was portioned between ethyl acetate (100 ml) and 0.5 N hydrochloric acid (100 ml). The separated organic layer was washed with 0.5 N hydrochloric acid (100 ml), water (100 ml), aqueous sodium bicarbonate (100 ml), water (100 ml) and brine (100 ml) successively, and dried over magnesium sulfate. Evaporation of the solvent gave 3-(N-t-butoxycarbonyl-N-methylamino)propanol (2.48 g) as an oil. The solution was concentrated in vacuo The separated organic layer was washed with 0.5 N hydrochloric acid (100 ml), water (100 ml), aqueous sodium bicarbonate (100 ml), water (100 ml) and brine (100 ml) successively dried over magnesium sulfate Evaporation of the solvent

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

実験手順: To a cooled (0° C.) solution of 3-(tert-butoxycarbonyl(methyl)amino)propanoic acid (1.095 g, max. 5.29 mmol) in extra dry MeOH (0.24 mL, 5.93 mmol) and DCM (5 mL) was added DMAP (0.066 g, 0.539 mmol). EDCI (1.239 g, 6.47 mmol) was added and the reaction mixture allowed to warm up to room temperature. The reaction mixture was washed with aqueous 0.5 N HCl (3×10 mL), and brine (25 mL). The organic phase was dried over Na2SO4, filtered, and evaporated in vacuo to afford the desired product (1.129 g, 98% over two steps) as a colourless oil. The reaction mixture was washed with aqueous 0.5 N HCl (3×10 mL), and brine (25 mL) The organic phase was dried over Na2SO4 filtered evaporated in vacuo

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

実験手順: To a solution of methyl 3-(tert-butoxycarbonyl(methyl)amino)propanoate (6.9 g, 0.0317 mol) in EtOH (15 mL) was added hydrazine monohydrate (7.7 mL, 0.158 mol) at rt. The reaction mixture was heated to 80° C. and stirred at 80° C. overnight. The reaction mixture was concentrated, and then DCM (300 mL) was added. The organic layer was washed with water and saturated sodium chloride, dried over Na2SO4, and concentrated to afford tert-butyl 3-hydrazinyl-3-oxopropyl(methyl)carbamate (6.8 g, 98%) as sticky oil, which was used directly in the next step. ESI-MS (EI+, m/z): 118 [M−100+H]+. The reaction mixture was concentrated DCM (300 mL) was added The organic layer was washed with water and saturated sodium chloride dried over Na2SO4 concentrated

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

実験手順: To a solution of 3-(tert-butoxycarbonyl(methyl)amino)propanoic acid (7.0 g, 0.032 mol) and K2CO3 (13.3 g, 0.096 mol) in DMF (100 mL) was added MeI (9.0 g, 0.064 mol) at rt. The resultant solution was stirred at rt for 3 hrs. The reaction mixture was quenched with ice water and extracted with ethyl acetate (2×). The combined organic layer was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (gradient elution 0%-10% EtOAc/petroleum ether) to afford methyl 3-(tert-butoxycarbonyl(methyl)amino)propanoate (6.9 g, 92%) as a white solid. ESI-MS (EI+, m/z): 118 [M−100+H]+. The reaction mixture was quenched with ice water extracted with ethyl acetate (2×) The combined organic layer was dried over Na2SO4 concentrated under reduced pressure The residue was purified by silica gel column chromatography (gradient elution 0%-10% EtOAc/petroleum ether)

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

実験手順: To a solution of methyl 3-(tert-butoxycarbonyl (methyl) amino)propanoate (6.9 g, 0.0317 mol) in EtOH (15 mL) was added hydrazine monohydrate (7.7 mL, 0.158 mol) at rt. The reaction mixture was heated to 80° C. and stirred at 80° C. overnight. The reaction mixture was concentrated, and then DCM (300 mL) was added. The organic layer was washed with water and saturated sodium chloride, dried over Na2SO4, and concenreated to afford tert-butyl 3-hydrazinyl-3-oxopropyl(methyl)carbamate (6.8 g, 98%) as sticky oil, which was used directly in the next step. ESI-MS (EI+, m/z): 118 [M-100+H]+. The reaction mixture was concentrated DCM (300 mL) was added The organic layer was washed with water and saturated sodium chloride dried over Na2SO4

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

実験手順: To a solution of 3-(tert-butoxycarbonyl(methyl)amino)propanoic acid (7.0 g, 0.032 mol) and K2CO3 (13.3 g, 0.096 mol) in DMF (100 mL) was added MeI (9.0 g, 0.064 mol) at rt. The resultant solution was stirred at rt for 3 hrs. The reaction mixture was quenched with ice water and extracted with ethyl acetate (2×). The combined organic layer was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (gradient elution 0%˜10% EtOAc/petroleum ether) to afford methyl 3-(tert-butoxycarbonyl (methyl) amino)propanoate (6.9 g, 92%) as a white solid. ESI-MS (EI+, m/z): 118 [M-100+H]+. The reaction mixture was quenched with ice water extracted with ethyl acetate (2×) The combined organic layer was dried over Na2SO4 concentrated under reduced pressure The residue was purified by silica gel column chromatography (gradient elution 0%˜10% EtOAc/petroleum ether)

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

実験手順: To a solution of N-t-butoxycarbonyl-N-methyl-β-alanine methyl ester (3.911 g) in methanol (20 ml) and water (20 ml) was added sodium borohydride (6.81 g) portionwise at 4° C. and the mixture was stirred at room temperature for 3 hours. The solution was concentrated in vacuo, and the residue was portioned between ethyl acetate (100 ml) and 0.5N hydrochloric acid (100 ml). The separated organic layer was washed with 0.5N hydrochloric acid (100 ml), water (100 ml), aqueous sodium bicarbonate (100 ml), water (100 ml) and brine (100 ml) successively,and dried over magnesium sulfate. Evaporation of the solvent gave 3-(N-t-butoxycarbonyl-N-methylamino)propanol (2.48 g) as an oil. The solution was concentrated in vacuo The separated organic layer was washed with 0.5N hydrochloric acid (100 ml), water (100 ml), aqueous sodium bicarbonate (100 ml), water (100 ml) and brine (100 ml) successively,and dried over magnesium sulfate Evaporation of the solvent

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

実験手順: To a solution of methyl 3-(tert-butoxycarbonyl(methyl)amino)propanoate (6.9 g, 0.0317 mol) in EtOH (15 mL) was added hydrazine monohydrate (7.7 mL, 0.158 mol) at rt. The reaction mixture was heated to 80° C. and stirred at 80° C. overnight. The reaction mixture was concentrated, and then DCM (300 mL) was added. The organic layer was washed with water and saturated sodium chloride, dried over Na2SO4, and concentrated to afford tert-butyl 3-hydrazinyl-3-oxopropyl(methyl)carbamate (6.8 g, 98%) as sticky oil, which was used directly in the next step. ESI-MS (EI+, m/z): 118 [M−100+H]+. The reaction mixture was concentrated DCM (300 mL) was added The organic layer was washed with water and saturated sodium chloride dried over Na2SO4 concentrated

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

実験手順: To a solution of 3-(tert-butoxycarbonyl(methyl)amino)propanoic acid (7.0 g, 0.032 mol) and K2CO3 (13.3 g, 0.096 mol) in DMF (100 mL) was added MeI (9.0 g, 0.064 mol) at rt. The resultant solution was stirred at rt for 3 hrs. The reaction mixture was quenched with ice water and extracted with ethyl acetate (2×). The combined organic layer was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (gradient elution 0%˜10% EtOAc/petroleum ether) to afford methyl 3-(tert-butoxycarbonyl(methyl)amino)propanoate (6.9 g, 92%) as a white solid. ESI-MS (EI+, m/z): 118 [M−100+H]+. The reaction mixture was quenched with ice water extracted with ethyl acetate (2×) The combined organic layer was dried over Na2SO4 concentrated under reduced pressure The residue was purified by silica gel column chromatography (gradient elution 0%˜10% EtOAc/petroleum ether)

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

実験手順: To a solution of methyl 3-(tert-butoxycarbonyl(methyl)amino)propanoate (6.9 g, 0.0317 mol) in EtOH (15 mL) was added hydrazine monohydrate (7.7 mL, 0.158 mol) at rt. The reaction mixture was heated to 80° C. and stirred at 80° C. overnight. The reaction mixture was concentrated, and then DCM (300 mL) was added. The organic layer was washed with water and saturated sodium chloride, dried over Na2SO4, and concentrated to afford tert-butyl 3-hydrazinyl-3-oxopropyl(methyl)carbamate (6.8 g, 98%) as sticky oil, which was used directly in the next step. ESI-MS (EI+, m/z): 118 [M−100+H]+. The reaction mixture was concentrated DCM (300 mL) was added The organic layer was washed with water and saturated sodium chloride dried over Na2SO4 concentrated

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

実験手順: To a solution of 3-(tert-butoxycarbonyl(methyl)amino)propanoic acid (7.0 g, 0.032 mol) and K2CO3 (13.3 g, 0.096 mol) in DMF (100 mL) was added MeI (9.0 g, 0.064 mol) at rt. The resultant solution was stirred at rt for 3 hrs. The reaction mixture was quenched with ice water and extracted with ethyl acetate (2×). The combined organic layer was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (gradient elution 0%˜10% EtOAc/petroleum ether) to afford methyl 3-(tert-butoxycarbonyl(methyl)amino)propanoate (6.9 g, 92%) as a white solid. ESI-MS (EI+, m/z): 118 [M−100+H]+. The reaction mixture was quenched with ice water extracted with ethyl acetate (2×) The combined organic layer was dried over Na2SO4 concentrated under reduced pressure The residue was purified by silica gel column chromatography (gradient elution 0%˜10% EtOAc/petroleum ether)