(2S)-2-methyl-3-phenylmethoxypropan-1-ol

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a thermometer, an N2 inlet, and a septum. The flask was charged with 24.050 g (0.189 mol) of oxalyl chloride and 425 mL CH2Cl2. The reaction mixture was stirred under an N2 atmosphere and cooled to −78° C. with an external dry ice-acetone bath. A solution of methyl sulfoxide (29.607 g; 0.379 mol) in 85 mL CH2Cl2 was then added over 5 min to the reaction mixture via cannula. After the adition, the reaction was stirred an additional 5 min and then a solution of 31.048 g (0.172 mol) of (S)-3-benzyloxy-2-methylpropan-1-ol in 170 mL CH2Cl2 was added via cannula. When the second addition was completed the reaction mixture was stirred for 15 min at −78° C. then 111.32 g (0.861 mol) of N,N-diisopropylethylamine was added via syringe. The reaction mixture was stirred an addition 15 min at −78° C., the cooling bath was removed and the reaction was allowed to warm. When the internal temperature had reached −15° C., 350 mL of a 10% aqueous NaHSO4 solution was slowly added and the mixture was transferred to a separatory funnel. The organic layer was separated, washed with aqueous NaHSO4 (2×250 mL), saturated NaCl, dried (MgSO4), filtered and evaporated. The residue was used immediately in the next step without further purification. An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer After the adition, the reaction was stirred an additional 5 min When the second addition was stirred for 15 min at −78° C. The reaction mixture was stirred an addition 15 min at −78° C. the cooling bath was removed to warm had reached −15° C. 350 mL of a 10% aqueous NaHSO4 solution was slowly added the mixture was transferred to a separatory funnel The organic layer was separated washed with aqueous NaHSO4 (2×250 mL), saturated NaCl dried (MgSO4) filtered evaporated The residue was used immediately in the next step without further purification

Conditions: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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

Conditions: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer, a thermometer, an N2 inlet, and a septum. The flask was charged with 24.050 g (0.189 mol) of oxalyl chloride and 425 mL CH2Cl2. The reaction mixture was stirred under an N2 atmosphere and cooled to −78° C. with an external dry ice-acetone bath. A solution of methyl sulfoxide (29.607 g; 0.379 mol) in 85 mL CH2Cl2 was then added over 5 min to the reaction mixture via cannula. After the adition, the reaction was stirred an additional 5 min and then a solution of 31.048 g (0.172 mol) of (S)-3-benzyloxy-2-methylpropan-1-ol in 170 mL CH2Cl2 was added via cannula. When the second addition was completed the reaction mixture was stirred for 15 min at −78° C. then 111.32 g (0.861 mol) of N,N-diisopropylethylamine was added via syringe. The reaction mixture was stirred an addition 15 min at −78° C., the cooling bath was removed and the reaction was allowed to warm. When the internal temperature had reached −15° C., 350 mL of a 10% aqueous NaHSO4 solution was slowly added and the mixture was transferred to a separatory funnel. The organic layer was separated, washed with aqueous NaHSO4 (2×250 mL), saturated NaCl, dried (MgSO4), filtered and evaporated. The residue was used immediately in the next step without further purification. An oven dried three-necked 2 L round bottom flask was equipped with a mechanical stirrer After the adition, the reaction was stirred an additional 5 min When the second addition was stirred for 15 min at −78° C. The reaction mixture was stirred an addition 15 min at −78° C. the cooling bath was removed to warm had reached −15° C. 350 mL of a 10% aqueous NaHSO4 solution was slowly added the mixture was transferred to a separatory funnel The organic layer was separated washed with aqueous NaHSO4 (2×250 mL), saturated NaCl dried (MgSO4) filtered evaporated The residue was used immediately in the next step without further purification

Conditions: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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