tert-butyl N-[(2R)-1-(dimethylamino)-1-oxopropan-2-yl]carbamate

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

実験手順: ((R)-1-Dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester (1.1 g, 5.1 mmol) was dissolved in 26 mL of cold 4M HCl in dioxane. After 1.5 h the reaction was evaporated to provide (R)-2-amino-N,N-dimethyl-propionamide hydrochloride which was used without further purification. After 1.5 h the reaction was evaporated

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

実験手順: (R)-2-(tert-Butoxycarbonylamino)propanoic acid (1.0 g, 5.3 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.8 g, 5.6 mmol) were dissolved in 13 mL of dichloromethane. Dimethylamine hydrochloride (0.64 g, 7.8 mmol) and N,N-diisopropylethylamine (3.6 mL, 20.8 mmol) were added and the mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with dichloromethane and water was added. The layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to give 1.16 g (100%) of ((R)-1-dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester. was added The layers were separated the aqueous layer was extracted once more with dichloromethane The combined organic layers were washed with sodium chloride solution dried over sodium sulfate concentrated The residue was purified by silica gel chromatography (ethyl acetate/hexanes)

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

実験手順: (R)-2-(tert-Butoxycarbonylamino)propanoic acid (1.0 g, 5.3 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.8 g, 5.6 mmol) were dissolved in 13 mL of dichloromethane. Dimethylamine hydrochloride (0.64 g, 7.8 mmol) and N,N-diisopropylethylamine (3.6 mL, 20.8 mmol) were added and the mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with dichloromethane and water was added. The layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to give 1.16 g (100%) of ((R)-1-dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester. was added The layers were separated the aqueous layer was extracted once more with dichloromethane The combined organic layers were washed with sodium chloride solution dried over sodium sulfate concentrated The residue was purified by silica gel chromatography (ethyl acetate/hexanes)

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

実験手順: Reduction was carried out according to Chem. Eur. J. (2008), 14(17), 51116-5119. To an ice-cooled lithium aluminum hydride (in Et2O) (21.35 mL, 21.35 mmol) solution was added drop wise a solution of ((R)-1-dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester (1.7105 g, 7.12 mmol) in Et2O (2-3 mL). The reaction mixture was stirred at 0° C. until disappearance of the starting material. The reaction mixture was carefully quenched by sequential addition of water (1.2 mL), 15% (w/w) NaOH (1.2 mL) and water (3.6 mL). Then EtOAc was added and the solids were filtered and washed with EtOAc. The filtrated was dried over MgSO4, filtered and evaporated off. Then the crude was dissolved in DCM, filtered and evaporated off to give 1.4543 g, 6.47 mmol, 91% yield ((R)-2-Dimethylamino-1-methyl-ethyl)-carbamic acid tert-butyl ester as yellowish oil. The crude was used without any further purification and characterization. The reaction mixture was carefully quenched by sequential addition of water (1.2 mL), 15% (w/w) NaOH (1.2 mL) and water (3.6 mL) Then EtOAc was added the solids were filtered washed with EtOAc The filtrated was dried over MgSO4 filtered evaporated off Then the crude was dissolved in DCM filtered evaporated off

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

実験手順: To a solution of (R)-2-tert-Butoxycarbonylamino-propionic acid (1.78 g, 9.43 mmol) in DCM (7.85 mL) was added portion wise DCC (2.14 g, 10.37 mmol) cooled in an ice bath. After stirring at room temperature for 30 min, dimethylamine (2 M in THF) (6.13 mL, 12.25 mmol) was added. The resulting solution was stirred overnight (18 h) until reaction was completed. The reaction mixture was filtered through silica gel and eluted with Ethyl acetate. Then the filtrate was evaporated off. The solvent was removed to yield (1.71 g, 7.12 mmol, 76% yield, 90% purity) ((R)-1-Dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester as a yellow oil. The product was used in the next step without further purification. cooled in an ice bath The resulting solution was stirred overnight (18 h) until reaction The reaction mixture was filtered through silica gel eluted with Ethyl acetate Then the filtrate was evaporated off The solvent was removed

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

実験手順: ((R)-1-Dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester (1.1 g, 5.1 mmol) was dissolved in 26 mL of cold 4M HCl in dioxane. After 1.5 h the reaction was evaporated to provide (R)-2-amino-N,N-dimethyl-propionamide hydrochloride which was used without further purification. After 1.5 h the reaction was evaporated

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

実験手順: (R)-2-(tert-Butoxycarbonylamino)propanoic acid (1.0 g, 5.3 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.8 g, 5.6 mmol) were dissolved in 13 mL of dichloromethane. Dimethylamine hydrochloride (0.64 g, 7.8 mmol) and N,N-diisopropylethylamine (3.6 mL, 20.8 mmol) were added and the mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with dichloromethane and water was added. The layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to give 1.16 g (100%) of ((R)-1-dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester. was added The layers were separated the aqueous layer was extracted once more with dichloromethane The combined organic layers were washed with sodium chloride solution dried over sodium sulfate concentrated The residue was purified by silica gel chromatography (ethyl acetate/hexanes)