苄基-(S)-罗氏酯

反应条件: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a reflux condenser and a 500 mL constant pressure addition funnel. The flask was charged with a solution of 62.252 g (0.299 mol) of methyl (S)-3-benzyloxy-2-methylpropanoate in 600 mL of anhydrous THF, and a 1.0 M solution of lithium aluminum hydride (300 mL; 0.3 mol) was transferred into the dropping funnel via a cannula. Stirring was started and the lithium aluminum hydride solution was added over 45 minutes to the reaction under an N2 atmosphere while the temperature of the reaction mixture was maintained between 25-30° C. using an external ice-water bath. After the addition was complete, the reaction was stirred an additional 6 h at room temperature at which point TLC analysis (20% EtOAc-hexane) indicated complete reaction. The reaction mixture was then cooled with an external ice-water bath and quenched by serial addition of 11.4 mL water, 11.4 mL of 15% aqueous NaOH, and 34.2 mL water. The reaction mixture was then filtered, the solids were washed with EtOAc, the filtrate and washings were combined and evaporated in vacuo. The residue was redissolved in EtOAc, washed with 10% aqueous NaHSO4, saturated NaCl, dried (MgSO4), filtered and evaporated. The residue was purified by Kugelrohr distillation to afford 47.67 g (89%) of the title compound as an oil. An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a reflux condenser and a 500 mL constant pressure addition funnel After the addition reaction The reaction mixture was then cooled with an external ice-water bath quenched by serial addition of 11.4 mL water, 11.4 mL of 15% aqueous NaOH, and 34.2 mL water The reaction mixture was then filtered the solids were washed with EtOAc evaporated in vacuo The residue was redissolved in EtOAc washed with 10% aqueous NaHSO4, saturated NaCl dried (MgSO4) filtered evaporated The residue was purified by Kugelrohr distillation

反应条件: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a reflux condenser and a 500 mL constant pressure addition funnel. The flask was charged with a solution of 62.252 g (0.299 mol) of methyl (S)-3-benzyloxy-2-methylpropanoate in 600 mL of anhydrous THF, and a 1.0 M solution of lithium aluminum hydride (300 mL; 0.3 mol) was transferred into the dropping funnel via a cannula. Stirring was started and the lithium aluminum hydride solution was added over 45 minutes to the reaction under an N2 atmosphere while the temperature of the reaction mixture was maintained between 25-30° C. using an external ice-water bath. After the addition was complete, the reaction was stirred an additional 6 h at room temperature at which point TLC analysis (20% EtOAc-hexane) indicated complete reaction. The reaction mixture was then cooled with an external ice-water bath and quenched by serial addition of 11.4 mL water, 11.4 mL of 15% aqueous NaOH, and 34.2 mL water. The reaction mixture was then filtered, the solids were washed with EtOAc, the filtrate and washings were combined and evaporated in vacuo. The residue was redissolved in EtOAc, washed with 10% aqueous NaHSO4, saturated NaCl, dried (MgSO4), filtered and evaporated. The residue was purified by Kugelrohr distillation to afford 47.67 g (89%) of the title compound as an oil. An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a reflux condenser and a 500 mL constant pressure addition funnel After the addition reaction The reaction mixture was then cooled with an external ice-water bath quenched by serial addition of 11.4 mL water, 11.4 mL of 15% aqueous NaOH, and 34.2 mL water The reaction mixture was then filtered the solids were washed with EtOAc evaporated in vacuo The residue was redissolved in EtOAc washed with 10% aqueous NaHSO4, saturated NaCl dried (MgSO4) filtered evaporated The residue was purified by Kugelrohr distillation

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

实验步骤: An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar and then charged sequentially with 15.948 g (0.135 mol) of (R)-(−)-methyl-3-hydroxy-2-methylpropanoate, carbon tetrachloride (150 mL), cyclohexane (300 mL), and 35.796 g (0.142 mol) of benzyl 2,2,2-trichloroacetimidate. Trifluoromethanesulfonic acid (0.8 mL; 9.0 mmol) was added to the solution and the resulting mixture was stirred for 16 h at room temperature under an N2 atmosphere. The reaction mixture was then filtered and the filtrate concentrated in vacuo. The residue was redissolved in 150 mL EtOAc and extracted with saturated aqueous NaHCO3 (1×100 mL). The organic layer was washed with saturated NaCl, dried (MgSO4), filtered and evaporated. The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane. The purified fractions were combined and evaporated in vacuo to afford 20.787 (74%) of the title compound as an oil. MS (CI): m/e=209 (M+1). An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar The reaction mixture was then filtered the filtrate concentrated in vacuo The residue was redissolved in 150 mL EtOAc extracted with saturated aqueous NaHCO3 (1×100 mL) The organic layer was washed with saturated NaCl dried (MgSO4) filtered evaporated The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane evaporated in vacuo

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

实验步骤: An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar and then charged sequentially with 15.948 g (0.135 mol) of (R)-(-)-methyl-3-hydroxy-2-methylpropanoate, carbon tetrachloride (150 mL), cyclohexane (300 mL), and 35.796 g (0.142 mol) of benzyl 2,2,2-trichloroacetimidate. Trifluoromethanesulfonic acid (0.8 mL; 9.0 mmol) was added to the solution and the resulting mixture was stirred for 16 h at room temperature under an N2 atmosphere. The reaction mixture was then filtered and the filtrate concentrated in vacuo. The residue was redissolved in 150 mL EtOAc and extracted with saturated aqueous NaHCO3 (lxlOO mL). The organic layer was washed with saturated NaCl, dried (MgSO4), filtered and evaporated. The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane. The purified fractions were combined and evaporated in vacuo to afford 20.787g of the title compound as an oil. MS (CI): m/e=209 (M+1). An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar The reaction mixture was then filtered the filtrate concentrated in vacuo The residue was redissolved in 150 mL EtOAc extracted with saturated aqueous NaHCO3 (lxlOO mL) The organic layer was washed with saturated NaCl dried (MgSO4) filtered evaporated The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane evaporated in vacuo

反应条件: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a reflux condenser and a 500 mL constant pressure addition funnel. The flask was charged with a solution of 62.252 g (0.299 mol) of methyl (S)-3-benzyloxy-2-methylpropanoate in 600 mL of anhydrous THF, and a 1.0 M solution of lithium aluminum hydride (300 mL; 0.3 mol) was transferred into the dropping funnel via a cannula. Stirring was started and the lithium aluminum hydride solution was added over 45 minutes to the reaction under an N2 atmosphere while the temperature of the reaction mixture was maintained between 25-30° C. using an external ice-water bath. After the addition was complete, the reaction was stirred an additional 6 h at room temperature at which point TLC analysis (20% EtOAc-hexane) indicated complete reaction. The reaction mixture was then cooled with an external ice-water bath and quenched by serial addition of 11.4 mL water, 11.4 mL of 15% aqueous NaOH, and 34.2 mL water. The reaction mixture was then filtered, the solids were washed with EtOAc, the filtrate and washings were combined and evaporated in vacuo. The residue was redissolved in EtOAc, washed with 10% aqueous NaHSO4, saturated NaCl, dried (MgSO4), filtered and evaporated. The residue was purified by Kugelrohr distillation to afford 47.67 g (89%) of the title compound as an oil. An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a reflux condenser and a 500 mL constant pressure addition funnel After the addition reaction The reaction mixture was then cooled with an external ice-water bath quenched by serial addition of 11.4 mL water, 11.4 mL of 15% aqueous NaOH, and 34.2 mL water The reaction mixture was then filtered the solids were washed with EtOAc evaporated in vacuo The residue was redissolved in EtOAc washed with 10% aqueous NaHSO4, saturated NaCl dried (MgSO4) filtered evaporated The residue was purified by Kugelrohr distillation

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

实验步骤: An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar and then charged sequentially with 15.948 g (0.135 mol) of (R)-(−)-methyl-3-hydroxy-2-methylpropanoate, carbon tetrachloride (150 mL), cyclohexane (300 mL), and 35.796 g (0.142 mol) of benzyl 2,2,2-trichloroacetimidate. Trifluoromethanesulfonic acid (0.8 mL; 9.0 mmol) was added to the solution and the resulting mixture was stirred for 16 h at room temperature under an N2 atmosphere. The reaction mixture was then filtered and the filtrate concentrated in vacuo. The residue was redissolved in 150 mL EtOAc and extracted with saturated aqueous NaHCO3 (1×100 mL). The organic layer was washed with saturated NaCl, dried (MgSO4), filtered and evaporated. The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane. The purified fractions were combined and evaporated in vacuo to afford 20.787 (74%) of the title compound as an oil. MS (CI): m/e=209 (M+1). An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar The reaction mixture was then filtered the filtrate concentrated in vacuo The residue was redissolved in 150 mL EtOAc extracted with saturated aqueous NaHCO3 (1×100 mL) The organic layer was washed with saturated NaCl dried (MgSO4) filtered evaporated The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane evaporated in vacuo