BENZYL (3-HYDROXY-2,2-DIMETHYLPROPYL)CARBAMATE

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a solution of 3-amino-2,2-dimethyl-1-propanol (2 g) in tetrahydrofuran (20 mL) was added N-(benzyloxycarbonyloxy)succinimide (7.25 g), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1-1/1) to give 3-benzyloxycarbonylamino-2,2-dimethyl-1-propanol (4.6 g) To this material were added carbon tetrachloride (40 mL), acetonitrile (40 mL), water (48 mL), sodium periodate (11.6 g) and ruthenium trichloride (0.2 g) successively, and the mixture was stirred at room temperature overnight. To the reaction mixture were added sodium periodate (11.6 g) and ruthenium trichloride (0.2 g), and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with water, and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in a saturated aqueous potassium carbonate solution. The solution was washed with ethyl acetate, and the aqueous layer was acidified with 2 mol/L hydrochloric acid. The mixture was extracted with ethyl acetate, and the extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-benzyloxycarbonylamino-2,2-di(methyl)propionic acid (3.6 g). This material was dissolved in tetrahydrofuran (25 mL). To the solution was added 1,1′-carbonylbis-1H-imidazole (3.39 g), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 28% aqueous ammonia solution (25 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water, and the resulting mixture was extracted with ethylacetate. The extract was washed with 1 mol/L hydrochloric acid, water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-benzyloxycarbonylamino-2,2-di(methyl)propionamide (3.35 g). The obtained 3-benzyloxycarbonylamino-2,2-di(methyl)propionamide (0.13 g) was dissolved in methanol (5 mL). To the solution was added 10% palladium-carbon powder (30 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (61 mg). the resulting mixture was extracted with ethyl acetate The extract was washed with water and brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1-1/1)

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

实验步骤: To a solution of 3-amino-2,2-dimethyl-1-propanol (2 g) in tetrahydrofuran (20 mL) was added N-(benzyloxycarbonyloxy)-succinimide (7.25 g), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1-1/1) to give 3-benzyloxycarbonylamino-2,2-dimethyl-1-propanol (4.6 g) To this material were added carbon tetrachloride (40 mL), acetonitrile (40 mL), water (48 mL), sodium periodate (11.6 g) and ruthenium trichloride (0.2 g) successively, and the mixture was stirred at room temperature overnight. To the reaction mixture were added sodium periodate (11.6 g) and ruthenium trichloride (0.2 g), and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with water, and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in a saturated aqueous potassium carbonate solution. The solution was washed with ethyl acetate, and the aqueous layer was acidified with 2 mol/L hydrochloric acid. The mixture was extracted with ethyl acetate, and the extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-benzyloxycarbonylamino-2,2-di(methyl)propionic acid (3.6 g). This material was dissolved in tetrahydrofuran (25 mL). To the solution was added 1,1′-carbonylbis-1H-imidazole (3.39 g), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 28% aqueous ammonia solution (25 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-benzyloxycarbonylamino-2,2-di(methyl)-propionamide (3.35 g). The obtained 3-benzyloxycarbonylamino-2,2-di(methyl)propionamide (0.13 g) was dissolved in methanol (5 mL). To the solution was added 10% palladium-carbon powder (30 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (61 mg). the resulting mixture was extracted with ethyl acetate The extract was washed with water and brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1-1/1)

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

实验步骤: 11.6 g of sodium periodate (54.2 mmol) and 0.2 g of ruthenium trichloride (0.96 mmol) were added to a solution of 4.6 g of 3-benzyloxycarbonylamino-2,2-di(methyl)propanol obtained in Reference Example (2a) (19.4 mmol) in a mixed solvent of carbon tetrachloride (40 ml), acetonitrile and water (40 ml), and the mixture was stirred at room temperature for 16 hours. 11.6 g of sodium periodate (54.2 mmol) and 0.2 g of ruthenium trichloride (0.96 mmol) were added to the reaction mixture, and the mixture was further stirred at room temperature for three days. The reaction mixture was diluted with water, followed by extraction with ethyl acetate. Then, the organic layer was dried over magnesium sulfate. After filtration, 300 ml of a saturated potassium carbonate aqueous solution was added to the residue, followed by washing with ethyl acetate. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to obtain 3.16 g of crude 3-benzyloxycarbonylamino-2,2-di(methyl)propionic acid. 3.0 g of 1,1′-carbonylbis-1H-imidazole (18.5 mmol) was added to a solution of 3.1 g of the crude 3-benzyloxycarbonylamino-2,2-di(methyl)propionic acid obtained above (12.3 mmol) in tetrahydrofuran (20 ml), and the mixture was stirred at room temperature for one hour. 20 ml of a 28% ammonia aqueous solution (914 mmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for one hour. The reaction mixture was diluted with water, followed by extraction with ethyl acetate. Then, the organic layer was washed with a 1 M hydrochloric acid aqueous solution and brine and dried over magnesium sulfate. After filtration, 300 ml of a saturated potassium carbonate aqueous solution was added to the residue, followed by washing with ethyl acetate. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:ethyl acetate/n-hexane=2/1-3/1) to obtain 2.54 g of the title compound (yield: 54%). the mixture was further stirred at room temperature for three days followed by extraction with ethyl acetate Then, the organic layer was dried over magnesium sulfate After filtration, 300 ml of a saturated potassium carbonate aqueous solution was added to the residue by washing with ethyl acetate followed by extraction with ethyl acetate Then, the organic layer was washed with brine dried over anhydrous magnesium sulfate After filtration the solvent was evaporated under reduced pressure

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

实验步骤: 50.0 g of N-(benzyloxycarbonyloxy)succinimide (200 mmol) was added to a solution of 13.8 g of 3-amino-2,2-dimethylpropanol (134 mmol) in tetrahydrofuran (140 ml), and the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure and diluted with water, followed by extraction with ethyl acetate. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: toluene/ethyl acetate=9/1-3/1) to obtain 29.52 g of the title compound (yield: 93%). The reaction mixture was concentrated under reduced pressure diluted with water followed by extraction with ethyl acetate Then, the organic layer was dried over anhydrous magnesium sulfate After filtration the solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (elution solvent: toluene/ethyl acetate=9/1-3/1)