叔-正丁基-[(1R)-2-羟基-1-苯乙基]氨基甲酸酯

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

实验步骤: 11 ml of pyridine and then 6.6 ml of methanesulfonyl chloride were added dropwise, at room temperature, to a solution containing 9.9 g of 2(R)-t-butoxycarbonylamino-2-phenylethanol [prepared as described in step (a) above] dissolved in 120 ml of methylene chloride. This mixture was stirred for 15 hours at room temperature, after which the solvent was removed by distillation. The residue was dissolved in ethyl acetate and water and the ethyl acetate layer was separated. This layer was washed with an aqueous solution of potassium hydrogen sulfate and an aqueous solution of sodium bicarbonate and then dried over anhydrous magnesium sulfate, after which the solvent was distilled off. The crystalline residue was collected by filtration and washed with a small amount of diisopropyl ether and cyclohexane to give 12.2 g of the title compound, melting at 108°-109° C. after which the solvent was removed by distillation The residue was dissolved in ethyl acetate water and the ethyl acetate layer was separated This layer was washed with an aqueous solution of potassium hydrogen sulfate an aqueous solution of sodium bicarbonate and then dried over anhydrous magnesium sulfate after which the solvent was distilled off The crystalline residue was collected by filtration washed with a small amount of diisopropyl ether and cyclohexane

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

实验步骤: 11 ml of pyridine and then 6.6 ml of methanesulfonyl chloride were added dropwise, at room temperature, to a solution containing 9.9 g of 2(R)-t-butoxycarbonylamino-2-phenylethanol [prepared as described in step (a) above] dissolved in 120 ml of methylene chloride. This mixture was stirred for 15 hours at room temperature, after which the solvent was removed by distillation. The residue was dissolved in ethyl acetate and water and the ethyl acetate layer was separated. This layer was washed with an aqueous solution of potassium hydrogen sulfate and an aqueous solution of sodium bicarbonate and then dried over anhydrous magnesium sulfate, after which the solvent was distilled off. The crystalline residue was collected by filtration and washed with a small amount of diisopropyl ether and cyclohexane to give 12.2 g of the title compound, melting at 108°-109° C. after which the solvent was removed by distillation The residue was dissolved in ethyl acetate water and the ethyl acetate layer was separated This layer was washed with an aqueous solution of potassium hydrogen sulfate an aqueous solution of sodium bicarbonate and then dried over anhydrous magnesium sulfate after which the solvent was distilled off The crystalline residue was collected by filtration washed with a small amount of diisopropyl ether and cyclohexane

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

实验步骤: To a solution of tert-butyl [(1R)-2-hydroxy-1-phenylethyl]carbamate (200 mg, 0.844 mmol) in CH2Cl2 (20 mL) at 0° C. was added Dess-Martin periodinane (447 mg, 1.05 mmol). The reaction was stirred at 0° C. for 15 minutes and then at room temperature for 30 minutes. The reaction was then diluted with EtOAc (75 mL) and washed rapidly with 10% K2CO3 (2×30 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue on a short column of silica gel with 50% EtOAc/hexanes gave tert-butyl [(1R)-2-oxo-1-phenylethyl]carbamate. 1H NMR (CDCl3, 600 MHz) (a major and a minor conformer observed). Data for major conformer given) δ 9.53 (s, 1H), 7.29-740 (m, 5H), 5.80 (bs, 1H), 5.31 (m, 1H), 1.42 (s, 91-1). This material was used immediately in the following reaction. at room temperature for 30 minutes washed rapidly with 10% K2CO3 (2×30 mL) The organic layer was dried over Na2SO4 filtered concentrated Purification of the residue on a short column of silica gel with 50% EtOAc/hexanes

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

实验步骤: To a solution of tert-butyl [(1R)-2-hydroxy-1-phenylethyl]carbamate (200 mg, 0.844 mmol) in CH2Cl2 (20 mL) at 0° C. was added Dess-Martin periodinane (447 mg, 1.05 mmol). The reaction was stirred at 0° C. for 15 minutes and then at room temperature for 30 minutes. The reaction was then diluted with EtOAc (75 mL) and washed rapidly with 10% K2CO3 (2×30 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue on a short column of silica gel with 50% EtOAc/hexanes gave tert-butyl [(1R)-2-oxo-1-phenylethyl]carbamate. 1H NMR (CDCl3, 600 MHz) (a major and a minor conformer observed). Data for major conformer given) δ 9.53 (s, 1H), 7.29-740 (m, 5H), 5.80 (bs, 1H), 5.31 (m, 1H), 1.42 (s, 91-1). This material was used immediately in the following reaction. at room temperature for 30 minutes washed rapidly with 10% K2CO3 (2×30 mL) The organic layer was dried over Na2SO4 filtered concentrated Purification of the residue on a short column of silica gel with 50% EtOAc/hexanes

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

实验步骤: To a solution of (2R)-2-amino-2-phenylethanol (400 mg, 2.91 mmol) in CH2Cl2 (15 mL) was added BOC2O (636 mg, 2.91 mmol) and DIPEA (507 μL, 2.91 mmol). The reaction was stirred at room temperature for 18 hours, diluted with EtOAc (75 mL) and washed with H2O, brine, 1N HCl, brine, saturated NaHCO3, and brine (25 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 50% EtOAc/hexanes afforded tert-butyl [(1R)-2-hydroxy-1-phenylethyl]carbamate. Rf=0.23 (40% EtOAc/hexane). 1H NMR (CDCl3, 600 MHz) δ 7.27-7.37 (m, 5H), 5.27 (bs, 1H), 4.78 (bs, 1H), 3.83 (bs, 2H), 2.46 (bs, 1H), 1.44 (bs, 9H). washed with H2O, brine, 1N HCl, brine, saturated NaHCO3, and brine (25 mL each) The organic layer was dried over Na2SO4 filtered concentrated Purification of the residue by flash chromatography with 50% EtOAc/hexanes

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

实验步骤: 1-(2,6-difluoro-benzyl)-5-nitro-1H-pyrimidine-2,4-dione (82 mg, 0.29 mmol), ((R)-2-hydroxy-1-phenyl-ethyl)-carbamic acid tert-butyl ester (69 mg, 0.29 mmol), and triphenylphosphine (114 mg, 0.44 mmol) were dissolved in anhydrous tetrahydrofuran (2 mL). To this solution was added diethyl azodicarboxylate (200 μl, 0.44 mmol), followed by stirring at room temperature for 4 hrs. The solution was concentrated, after which the residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate/dichloromethane, 3/1/1) and dried in a vacuum to afford 67 mg of the compound as a colorless oil (yield 67%). 1H NMR (300 MHz, CDCl3) δ 1.30 (9H, s), 3.40 (1H, d), 4.50 (1H, m), 5.08-5.27 (4H, m), 7.02 (2H, t), 7.26-7.47 (6H, m), 8.78 (1H, s) The solution was concentrated after which the residue was purified dried in a vacuum

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

实验步骤: 5-Bromo-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dione (synthesized according to the method of BMCL 2004 14(19) 4967-4973) (2.77 g, 8.37 mmol), ((R)-2-hydroxy-1-phenyl-ethyl)-carbamic acid tert-butyl ester (2.08 g, 8.78 mmol), and triphenylphosphine (3.29 g, 12.5 mmol) were added to anhydrous tetrahydrofuran (70 mL) and stirred for a short time. To this solution was slowly added diethylazodicarboxylate (1.95 mL, 12.5 mmol), followed by stirring at room temperature for 12 hrs in a nitrogen atmosphere. Following concentration, the residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate, 2/1) and dried in a vacuum to afford 2.26 g of the compound as a white foam (yield 49%). by stirring at room temperature for 12 hrs in a nitrogen atmosphere concentration the residue was purified dried in a vacuum

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

实验步骤: 5-Bromo-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dione (synthesized according to the method of BMCL 2004 14(19) 4967-4973) (2.77 g, 8.37 mmol), ((R)-2-hydroxy-1-phenyl-ethyl)-carbamic acid tert-butyl ester (2.08 g, 8.78 mmol), and triphenylphosphine (3.29 g, 12.5 mmol) were added to anhydrous tetrahydrofuran (70 mL) and stirred for a short time. To this solution was slowly added diethylazodicarboxylate (1.95 mL, 12.5 mmol), followed by stirring at room temperature for 12 hrs in a nitrogen atmosphere. Following concentration, the residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate, 2/1) and dried in a vacuum to afford 2.26 g of the compound as a white foam (yield 49%). by stirring at room temperature for 12 hrs in a nitrogen atmosphere concentration the residue was purified dried in a vacuum

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

实验步骤: 11 ml of pyridine and then 6.6 ml of methanesulfonyl chloride were added dropwise, at room temperature, to a solution containing 9.9 g of 2(R)-t-butoxycarbonylamino-2-phenylethanol [prepared as described in step (a) above] dissolved in 120 ml of methylene chloride. This mixture was stirred for 15 hours at room temperature, after which the solvent was removed by distillation. The residue was dissolved in ethyl acetate and water and the ethyl acetate layer was separated. This layer was washed with an aqueous solution of potassium hydrogen sulfate and an aqueous solution of sodium bicarbonate and then dried over anhydrous magnesium sulfate, after which the solvent was distilled off. The crystalline residue was collected by filtration and washed with a small amount of diisopropyl ether and cyclohexane to give 12.2 g of the title compound, melting at 108°-109° C. after which the solvent was removed by distillation The residue was dissolved in ethyl acetate water and the ethyl acetate layer was separated This layer was washed with an aqueous solution of potassium hydrogen sulfate an aqueous solution of sodium bicarbonate and then dried over anhydrous magnesium sulfate after which the solvent was distilled off The crystalline residue was collected by filtration washed with a small amount of diisopropyl ether and cyclohexane

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1 g of N-methyl-2-nitrobenzenesulfonamide, 2.3 g of tert-butyl [(1R)-2-hydroxy-1-phenylethyl]carbamate, 2.5 g of triphenylphosphine, 4.2 ml of diethyl azodicarboxylate, and 40 ml of toluene was stirred at 80° C. for 2 hours, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in chloroform was added silica gel, followed by filtration, and the filtrate was concentrated under reduced pressure. To a solution of the obtained residue in 3 ml of dichloromethane was added 3 ml of trifluoroacetic acid, followed by stirring for 1 hour. The solvent was evaporated under reduced pressure, and an aqueous sodium carbonate solution and chloroform were then added thereto to carry out a layer separation operation. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 890 mg of N-[(2R)-2-amino-2-phenylethyl]-N-methyl-2-nitrobenzenesulfonamide. the solvent was evaporated under reduced pressure To a solution of the obtained residue in chloroform was added silica gel followed by filtration the filtrate was concentrated under reduced pressure To a solution of the obtained residue in 3 ml of dichloromethane was added 3 ml of trifluoroacetic acid by stirring for 1 hour The solvent was evaporated under reduced pressure an aqueous sodium carbonate solution and chloroform were then added a layer separation operation The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1 g of N-methyl-2-nitrobenzenesulfonamide, 2.3 g of tert-butyl [(1R)-2-hydroxy-1-phenylethyl]carbamate, 2.5 g of triphenylphosphine, 4.2 ml of diethyl azodicarboxylate, and 40 ml of toluene was stirred at 80° C. for 2 hours, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in chloroform was added silica gel, followed by filtration, and the filtrate was concentrated under reduced pressure. To a solution of the obtained residue in 3 ml of dichloromethane was added 3 ml of trifluoroacetic acid, followed by stirring for 1 hour. The solvent was evaporated under reduced pressure, and an aqueous sodium carbonate solution and chloroform were then added thereto to carry out a layer separation operation. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 890 mg of N-[(2R)-2-amino-2-phenylethyl]-N-methyl-2-nitrobenzenesulfonamide. the solvent was evaporated under reduced pressure To a solution of the obtained residue in chloroform was added silica gel followed by filtration the filtrate was concentrated under reduced pressure To a solution of the obtained residue in 3 ml of dichloromethane was added 3 ml of trifluoroacetic acid by stirring for 1 hour The solvent was evaporated under reduced pressure an aqueous sodium carbonate solution and chloroform were then added a layer separation operation The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

实验步骤: To a solution of tert-butyl [(1R)-2-hydroxy-1-phenylethyl]carbamate (200 mg, 0.844 mmol) in CH2Cl2 (20 mL) at 0° C. was added Dess-Martin periodinane (447 mg, 1.05 mmol). The reaction was stirred at 0° C. for 15 minutes and then at room temperature for 30 minutes. The reaction was then diluted with EtOAc (75 mL) and washed rapidly with 10% K2CO3 (2×30 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue on a short column of silica gel with 50% EtOAc/hexanes gave tert-butyl [(1R)-2-oxo-1-phenylethyl]carbamate. 1H NMR (CDCl3, 600 MHz) (a major and a minor conformer observed). Data for major conformer given) δ 9.53 (s, 1H), 7.29-7.40 (m, 5H), 5.80 (bs, 1H), 5.31 (m, 1H), 1.42 (s, 9H). This material was used immediately in the following reaction. at room temperature for 30 minutes washed rapidly with 10% K2CO3 (2×30 mL) The organic layer was dried over Na2SO4 filtered concentrated Purification of the residue on a short column of silica gel with 50% EtOAc/hexanes