tert-butyl N-[(2R,3R)-1-hydroxy-3-phenylmethoxybutan-2-yl]carbamate

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

Procedure: To a solution of ((1R,2R)-2-benzyloxy-1-hydroxymethylpropyl)carbamic acid t-butyl ester (83.1 g, CAS No. 133565-43-2) in toluene (400 mL) was added tetrabutylammonium hydrogen sulfate (24.1 g) in 50% aqueous sodium hydroxide (400 mL). t-Butylbromoacetate (125 mL) was dropwise added to the resultant solution while cooling with ice, and this solution was stirred at the same temperature for 3 hours. Then, water (500 mL) and toluene (500 mL) was added to the solution. The organic layer was separated and washed with brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, to thereby obtain a crude product (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butylcarbonylaminobutoxy)acetic acid t-butyl ester. To a solution of the obtained crude product (118g) in dichloromethane (315 mL) was added trifluoroacetic acid (315 mL), and the resultant solution was stirred for 2 hours at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (350 mL). To the resultant solution was dropwise added thionyl chloride (96.9 mL) while cooling with ice, and then the solution was stirred for 1 hour at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (315 mL). To the resultant solution was then dropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with ethyl acetate and water. The organic layer was partitioned and successively washed with 1 N hydrochloric acid and brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting product was purified by silica gel column chromatography (ethyl acetate), to thereby obtain the titled compound (61.57 g). The physical properties of the compound were as follows. while cooling with ice The organic layer was separated washed with brine The organic layer was then dried over anhydrous magnesium sulfate Solvent was removed by distillation under reduced pressure to thereby obtain a crude product (122.5 g) Solvent was removed by distillation under reduced pressure the resultant product was diluted with methanol (350 mL) while cooling with ice the solution was stirred for 1 hour at room temperature Solvent was removed by distillation under reduced pressure the resultant product was diluted with methanol (315 mL) dropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice Solvent was removed by distillation under reduced pressure the resultant product was diluted with ethyl acetate and water The organic layer was partitioned successively washed with 1 N hydrochloric acid and brine The organic layer was then dried over anhydrous magnesium sulfate Solvent was removed by distillation under reduced pressure the resulting product was purified by silica gel column chromatography (ethyl acetate)

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

Procedure: To a solution of ((1R,2R)-2-benzyloxy-1-hydroxymethylpropyl)carbamic acid t-butyl ester (83.1 g, CAS No. 133565-43-2) in toluene (400 mL) was added tetrabutylammonium hydrogen sulfate (24.1 g) in 50% aqueous sodium hydroxide (400 mL). t-Butylbromoacetate (125 mL) was dropwise added to the resultant solution while cooling with ice, and this solution was stirred at the same temperature for 3 hours. Then, water (500 mL) and toluene (500 mL) was added to the solution. The organic layer was separated and washed with brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, to thereby obtain a crude product (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butylcarbonylaminobutoxy)acetic acid t-butyl ester. To a solution of the obtained crude product (118g) in dichloromethane (315 mL) was added trifluoroacetic acid (315 mL), and the resultant solution was stirred for 2 hours at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (350 mL). To the resultant solution was dropwise added thionyl chloride (96.9 mL) while cooling with ice, and then the solution was stirred for 1 hour at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (315 mL). To the resultant solution was then dropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with ethyl acetate and water. The organic layer was partitioned and successively washed with 1 N hydrochloric acid and brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting product was purified by silica gel column chromatography (ethyl acetate), to thereby obtain the titled compound (61.57 g). The physical properties of the compound were as follows. while cooling with ice The organic layer was separated washed with brine The organic layer was then dried over anhydrous magnesium sulfate Solvent was removed by distillation under reduced pressure to thereby obtain a crude product (122.5 g) Solvent was removed by distillation under reduced pressure the resultant product was diluted with methanol (350 mL) while cooling with ice the solution was stirred for 1 hour at room temperature Solvent was removed by distillation under reduced pressure the resultant product was diluted with methanol (315 mL) dropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice Solvent was removed by distillation under reduced pressure the resultant product was diluted with ethyl acetate and water The organic layer was partitioned successively washed with 1 N hydrochloric acid and brine The organic layer was then dried over anhydrous magnesium sulfate Solvent was removed by distillation under reduced pressure the resulting product was purified by silica gel column chromatography (ethyl acetate)

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

Procedure: A 50% sodium hydroxide solution (400 mL) and tetrabutylammoniumbisulfate (24.1 g) were added to a toluene (400 mL) solution of ((1R,2R)-2-benzyloxy-1-hydroxymethylpropyl) carbamic acid t-butyl ester (83.1 g, CAS#133565-43-2). Under ice-cooling, t-butyl bromoacetic acid ester (125 mL) was added dropwise, and stirring was continued for 3 hours at the same temperature. Water (500 mL) and toluene (500 mL) were added, and the organic layer was partitioned, and the resultant was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under a vacuum, and a crude material (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butoxycarbonylaminobutoxy)acetic acid t-butyl ester was obtained. Dichloromethane (315 mL) and trifluoroacetic acid (315 mL) were added to the obtained crude material (118 q), and stirring was continued for 2 hours at room temperature. The solvent was removed under a vacuum, and methanol (350 mL) was added. Under ice-cooling, thionyl chloride (96.9 mL) was added dropwise, and the resultant was stirred at room temperature for 1 hour. The solvent was removed under a vacuum, and methanol (315 mL) was added, and under ice-cooling, sodium methoxide (165 mL, 28% methanol solution) was added dropwise. The solvent was removed under a vacuum, and ethyl acetate and water were added, and the organic layer was partitioned. The organic layer was washed with 1 N hydrochloric acid and brine in sequence, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed under a vacuum, and the resultant was purified by silica gel column chromatography (ethyl acetate), and the title compound (61.57 g) was obtained. The physical property values are as follows. Under ice-cooling the organic layer was partitioned the resultant was washed with brine The organic layer was dried over anhydrous magnesium sulfate the solvent was removed under a vacuum a crude material (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butoxycarbonylaminobutoxy)acetic acid t-butyl ester was obtained obtained crude material (118 q) stirring was continued for 2 hours at room temperature The solvent was removed under a vacuum, and methanol (350 mL) was added Under ice-cooling thionyl chloride (96.9 mL) was added dropwise the resultant was stirred at room temperature for 1 hour The solvent was removed under a vacuum, and methanol (315 mL) was added under ice-cooling sodium methoxide (165 mL, 28% methanol solution) was added dropwise The solvent was removed under a vacuum, and ethyl acetate and water were added the organic layer was partitioned The organic layer was washed with 1 N hydrochloric acid and brine in sequence the organic layer was dried over anhydrous magnesium sulfate The solvent was removed under a vacuum the resultant was purified by silica gel column chromatography (ethyl acetate)

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

Procedure: To a suspension of lithium aluminum hydride (2.94 g, 78 mmol) in 50 mL diethyl ether at 0° C. was slowly added a solution of (2S,3R)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)butanoic acid (8.0 g, 25.9 mmol) in 25 mL diethyl ether. The reaction was allowed to warm to rt and stirred 1 hr. Water (3 ml) was added with caution, to the reaction mixture. This addition was followed by an addition of 15% NaOH (3 ml) and water (9 ml). These additions were made with extreme caution to control the rate of gas evolution. After stirring 1 hr at rt, MgSO4 was added and the mixture was filtered. The filtrate was concentrated to afford an oil, which was chromatographed on a 120 gm Isco cartridge using an 0-75% EtOAc/Hex gradient. The pure fractions were concentrated to afford tert-butyl((2R,3R)-3-(benzyloxy)-1-hydroxybutan-2-yl)carbamate (5.44 g, 18.42 mmol, 71.2% yield) as a colorless oil. 1H NMR (400 MHz, CCl3D) δ 7.32 (s, 5H), 5.07 (br. s., 1H), 4.64 (d, J=11.4 Hz, 1H), 4.38 (d, J=11.7 Hz, 1H), 3.83 (d, J=6.2 Hz, 1H), 3.79-3.71 (m, 1H), 3.70-3.59 (m, 2H), 2.60-2.38 (m, 1H), 1.48-1.42 (m, 9H), 1.27-1.25 (m, 3H). This addition After stirring 1 hr at rt the mixture was filtered The filtrate was concentrated to afford an oil, which was chromatographed on a 120 gm Isco cartridge The pure fractions were concentrated

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

Procedure: To a solution of ((1R,2R)-2-benzyloxy-1-hydroxymethylpropyl)carbamic acid t-butyl ester (83.1 g, CAS No. 133565-43-2) in toluene (400 mL) was added tetrabutylammonium hydrogen sulfate (24.1 g) in 50% aqueous sodium hydroxide (400 mL). t-Butylbromoacetate (125 mL) was dropwise added to the resultant solution while cooling with ice, and this solution was stirred at the same temperature for 3 hours. Then, water (500 mL) and toluene (500 mL) was added to the solution. The organic layer was separated and washed with brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, to thereby obtain a crude product (122.5 g) containing ((2R,3R)-3-benzyloxy-2-t-butylcarbonylaminobutoxy)acetic acid t-butyl ester. To a solution of the obtained crude product (118g) in dichloromethane (315 mL) was added trifluoroacetic acid (315 mL), and the resultant solution was stirred for 2 hours at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (350 mL). To the resultant solution was dropwise added thionyl chloride (96.9 mL) while cooling with ice, and then the solution was stirred for 1 hour at room temperature. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (315 mL). To the resultant solution was then dropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with ethyl acetate and water. The organic layer was partitioned and successively washed with 1 N hydrochloric acid and brine. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting product was purified by silica gel column chromatography (ethyl acetate), to thereby obtain the titled compound (61.57 g). The physical properties of the compound were as follows. while cooling with ice The organic layer was separated washed with brine The organic layer was then dried over anhydrous magnesium sulfate Solvent was removed by distillation under reduced pressure to thereby obtain a crude product (122.5 g) Solvent was removed by distillation under reduced pressure the resultant product was diluted with methanol (350 mL) while cooling with ice the solution was stirred for 1 hour at room temperature Solvent was removed by distillation under reduced pressure the resultant product was diluted with methanol (315 mL) dropwise added sodium methoxide (165 mL, 28% methanol solution) while cooling with ice Solvent was removed by distillation under reduced pressure the resultant product was diluted with ethyl acetate and water The organic layer was partitioned successively washed with 1 N hydrochloric acid and brine The organic layer was then dried over anhydrous magnesium sulfate Solvent was removed by distillation under reduced pressure the resulting product was purified by silica gel column chromatography (ethyl acetate)