benzyl N-[(2S)-1-hydroxy-3-methylbutan-2-yl]carbamate

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

実験手順: To a stirred solution of N-benzyloxycarbonyl-L-valinol (8.80 g, 0.037 mol) and triethylamine (30.00 g, 41.3 mL, 0.30 mol) in 100 mL dimethylsulfoxide under a nitrogen atmosphere was added a solution of sulfur trioxide pyridine complex (20.62 g, 0.130 mol) in dimethylsulfoxide (100 mL) dropwise via an addition funnel. An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition. After 30 min the cooling bath was removed and the reaction was allowed to warm to room temperature over 2 h. The brown solution was acidified with cold 2N HCl to approximately pH 2 and extracted with ether (3×150 mL). The combined organic layers were washed with brine, dried (anhydrous magnesium sulfate) and evaporated to give 7.40 g of N-benzyloxycarbonyl-L-valinal (84.8%) as a yellow oil. The resulting material can be used without purification or further purified using column chromatography (silica gel, 9:1 hexanes:ethyl acetate). An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition After 30 min the cooling bath was removed extracted with ether (3×150 mL) The combined organic layers were washed with brine dried (anhydrous magnesium sulfate) evaporated

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

実験手順: To a stirred solution of valinol (13.96 g, 0.14 mol) and triethylamine (18.87 mL, 0.14 mol) in 250 mL of dry methylene chloride cooled to 0° C. under a nitrogen atmosphere was added 19.3 mL (0.14 mol) of benzyl chloroformate dropwise over 20 min. After warming to RT overnight, the mixture was diluted with methylene chloride (100 mL) and washed with 1N HCl (2X), brine and dried with anhydrous magnesium sulfate. The resulting mixture was filtered and evaporated to give 30.70 g (95.6%) of N-benzyloxycarbonyl-valinol as a white solid: Rf =0.27 (silica gel; 1:1 hexane:ethyl acetate). Used without further purification. washed with 1N HCl (2X), brine dried with anhydrous magnesium sulfate The resulting mixture was filtered evaporated

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

実験手順: Benzyl chloroformate (91.0 g, 95% purity) was added dropwise over a period of 1 h to a precooled (0° C.) solution of L-valinol (50.0 g) and triethylamine (60.0 g) in chloroform (1500 ml). The reaction mixture was stirred for 1 h at 0° C. and then allowed to warm to,room temperature over 2 h. After the reaction mixture was evaporated, ethyl acetate (1500 ml) was added to the residue and the organic solution was washed (1N NaOH, brine), dried (MgSO4), and evaporated. The residue was purified by flash chromatography, using a stepwise gradient elution of ether:hexane (1:5) followed by ether, to give the alcohol (91.4 g) as a white waxy solid; TLC, Rf =0.23, hexane:ethanol (50:50). to warm to,room temperature over 2 h After the reaction mixture was evaporated ethyl acetate (1500 ml) was added to the residue the organic solution was washed (1N NaOH, brine) dried (MgSO4) evaporated The residue was purified by flash chromatography a stepwise gradient elution of ether:hexane (1:5)

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

実験手順: Subsequently, to a solution of [(1S)-1-(hydroxymethyl)-2-methylpropyl]carbamic acid benzyl ester (4.56 g, 19.2 mmol) in dimethylformamide (140 ml) were added t-butyldiphenylsilyl chloride (6.00 ml, 23.1 mmol) and imidazole (1.57 g, 23.1 mmol) in an ice bath, and the resulting mixture was stirred at room temperature for 4 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (8:1→6:1) as the eluant to afford [(1S)-1-(t-butyldiphenylsilyloxy)-2-methyl-propyl]-carbamic acid benzyl ester (10.1 g, yield 100%) as white crystals. the completion of the reaction the reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a silica gel column

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

実験手順: Subsequently, to a solution of [(1S)-1-(hydroxymethyl)-2-methylpropyl]carbamic acid benzyl ester (4.56 g, 19.2 mmol) in dimethylformamide (140 ml) were added t-butyldiphenylsilyl chloride (6.00 ml, 23.1 mmol) and imidazole (1.57 g, 23.1 mmol) in an ice bath, and the resulting mixture was stirred at room temperature for 4 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (8:1→6:1) as the eluant to afford [(1S)-1-(t-butyldiphenylsilyloxy)-2-methyl-propyl]-carbamic acid benzyl ester (10.1 g, yield 100%) as white crystals. the completion of the reaction the reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a silica gel column

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

実験手順: To a solution of L-valinol (2.00 g, 19.4 mmol) in methylene chloride (60 ml) were added chloroformic acid benzyl ester (3.32 ml, 23.3 mmol) and triethylamine (3.27 ml, 23.3 mmol) in an ice bath, and the mixture was stirred at room temperature for 4.5 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The obtained organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (2:1→1:2) as the eluant to afford [(1S)-1-(hydroxymethyl)-2-methylpropyl]carbamic acid benzyl ester (4.56 g, yield 99%) as white crystals. the completion of the reaction the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution The obtained organic layer was washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by chromatography on a silica gel column

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

実験手順: To a stirred solution of N-benzyloxycarbonyl-L-valinol (8.80 g, 0.037 mol) and triethylamine (30.00 g, 41.3 mL, 0.30 mol) in 100 mL dimethylsulfoxide under a nitrogen atmosphere was added a solution of sulfur trioxide pyridine complex (20.62 g, 0.130 mol) in dimethylsulfoxide (100 mL) dropwise via an addition funnel. An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition. After 30 min the cooling bath was removed and the reaction was allowed to warm to room temperature over 2 h. The brown solution was acidified with cold 2N HCl to approximately pH 2 and extracted with ether (3×150 mL). The combined organic layers were washed with brine, dried (anhydrous magnesium sulfate) and evaporated to give 7.40 g of N-benzyloxycarbonyl-L-valinal (84.8%) as a yellow oil. The resulting material can be used without purification or further purified using column chromatography (silica gel, 9:1 hexanes:ethyl acetate). An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition After 30 min the cooling bath was removed extracted with ether (3×150 mL) The combined organic layers were washed with brine dried (anhydrous magnesium sulfate) evaporated

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

実験手順: To a stirred solution of valinol (13.96 g, 0.14 mol) and triethylamine (18.87 mL, 0.14 mol) in 250 mL of dry methylene chloride cooled to 0° C. under a nitrogen atmosphere was added 19.3 mL (0.14 mol) of benzyl chloroformate dropwise over 20 min. After warming to RT overnight, the mixture was diluted with methylene chloride (100 mL) and washed with 1N HCl (2X), brine and dried with anhydrous magnesium sulfate. The resulting mixture was filtered and evaporated to give 30.70 g (95.6%) of N-benzyloxycarbonyl-valinol as a white solid: Rf =0.27 (silica gel; 1:1 hexane:ethyl acetate). Used without further purification. washed with 1N HCl (2X), brine dried with anhydrous magnesium sulfate The resulting mixture was filtered evaporated

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

実験手順: To a stirred solution of N-benzyloxycarbonyl-L-valinol (8.80 g, 0.037 mol) and triethylamine (30.00 g, 41.3 mL, 0.30 mol) in 100 mL dimethylsulfoxide under a nitrogen atmosphere was added a solution of sulfur trioxide pyridine complex (20.62 g, 0.130 mol) in dimethylsulfoxide (100 mL) dropwise via an addition funnel. An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition. After 30 min the cooling bath was removed and the reaction was allowed to warm to room temperature over 2 h. The brown solution was acidified with cold 2N HCl to approximately pH 2 and extracted with ether (3×150 mL). The combined organic layers were washed with brine, dried (anhydrous magnesium sulfate) and evaporated to give 7.40 g of N-benzyloxycarbonyl-L-valinal (84.8%) as a yellow oil. The resulting material can be used without purification or further purified using column chromatography (silica gel, 9:1 hexanes:ethyl acetate). An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition After 30 min the cooling bath was removed extracted with ether (3×150 mL) The combined organic layers were washed with brine dried (anhydrous magnesium sulfate) evaporated

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

実験手順: Benzyl chloroformate (91.0 g, 95% purity) was added dropwise over a period of 1 h to a precooled (0° C.) solution of L-valinol (50.0 g) and triethylamine (60.0 g) in chloroform (1500 ml). The reaction mixture was stirred for 1 h at 0° C. and then allowed to warm to,room temperature over 2 h. After the reaction mixture was evaporated, ethyl acetate (1500 ml) was added to the residue and the organic solution was washed (1N NaOH, brine), dried (MgSO4), and evaporated. The residue was purified by flash chromatography, using a stepwise gradient elution of ether:hexane (1:5) followed by ether, to give the alcohol (91.4 g) as a white waxy solid; TLC, Rf =0.23, hexane:ethanol (50:50). to warm to,room temperature over 2 h After the reaction mixture was evaporated ethyl acetate (1500 ml) was added to the residue the organic solution was washed (1N NaOH, brine) dried (MgSO4) evaporated The residue was purified by flash chromatography a stepwise gradient elution of ether:hexane (1:5)

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

実験手順: Benzyl chloroformate (91.0 g, 95% purity) was added dropwise over a period of 1 h to a precooled (0° C.) solution of L-valinol (50.0 g) and triethylamine (60.0 g) in chloroform (1500 ml). The reaction mixture was stirred for 1 h at 0° C. and then allowed to warm to,room temperature over 2 h. After the reaction mixture was evaporated, ethyl acetate (1500 ml) was added to the residue and the organic solution was washed (1N NaOH, brine), dried (MgSO4), and evaporated. The residue was purified by flash chromatography, using a stepwise gradient elution of ether:hexane (1:5) followed by ether, to give the alcohol (91.4 g) as a white waxy solid; TLC, Rf =0.23, hexane:ethanol (50:50). to warm to,room temperature over 2 h After the reaction mixture was evaporated ethyl acetate (1500 ml) was added to the residue the organic solution was washed (1N NaOH, brine) dried (MgSO4) evaporated The residue was purified by flash chromatography a stepwise gradient elution of ether:hexane (1:5)

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

実験手順: To a stirred solution of N-benzyloxycarbonyl-L-valinol (8.80 g, 0.037 mol) and triethylamine (30.00 g, 41.3 mL, 0.30 mol) in 100 mL dimethylsulfoxide under a nitrogen atmosphere was added a solution of sulfur trioxide pyridine complex (20.62 g, 0.130 mol) in dimethylsulfoxide (100 mL) dropwise via an addition funnel. An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition. After 30 min the cooling bath was removed and the reaction was allowed to warm to room temperature over 2 h. The brown solution was acidified with cold 2 N HCl to approximately pH 2 and extracted with ether (3×150 mL). The combined organic layers were washed with brine, dried (anhydrous magnesium sulfate) and evaporated to give 7.40 g of N-benzyloxycarbonyl-L-valinal (84.8%) as a yellow oil. The resulting material can be used without purification or further purified using column chromatography (silica gel, 9:1 hexanes:ethyl acetate). An ice water bath was used to maintain the temperature of the reaction mixture below room temperature during the addition After 30 min the cooling bath was removed extracted with ether (3×150 mL) The combined organic layers were washed with brine dried (anhydrous magnesium sulfate) evaporated