benzyl N-[(2S)-1-hydroxypropan-2-yl]carbamate

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

Procedure: Dimethylsulfoxide (1.01 g, 918 μL, 12.9 mmol) was added dropwise to a stirred solution of oxalyl chloride (790 mg, 543 μL, 6.23 mmol) in dry CH2Cl2 (12.6 mL) at −78° C. under N2 and the reaction was stirred for 15 min. A solution of benzyl [(1S)-2-hydroxy-1-methylethyl]carbamate (965 mg, 4.61 mmol) in dry CH2Cl2 (12.6 mL) was added dropwise by cannula and the mixture was stirred at −78° C. for 30 min. Triethylamine (1.34 g, 1.85 mL, 13.2 mmol) was added and the reaction was allowed to warm to room temperature and was stirred for 2 h. Water (15 mL) was added and the aqueous phase was separated and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were washed with saturated NaHCO3 and brine, then dried (MgSO4) and concentrated in vacuo to afford benzyl [(1S)-1-methyl-2-oxoethyl]carbamate as a colorless oil. Rf=0.75 (50% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3) δ 9.58 (s, 1H), 7.39-7.35 (m, 5H), 5.39 (br s, 1H), 5.15 (s, 2H), 4.33 (m, 1H), 1.40 (d, J=7.1 Hz, 3H). the mixture was stirred at −78° C. for 30 min was stirred for 2 h the aqueous phase was separated extracted with CH2Cl2 (3×15 mL) The combined organic extracts were washed with saturated NaHCO3 and brine dried (MgSO4) concentrated in vacuo

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

Procedure: Dimethylsulfoxide (1.01 g, 918 μL, 12.9 mmol) was added dropwise to a stirred solution of oxalyl chloride (790 mg, 543 μL, 6.23 mmol) in dry CH2Cl2 (12.6 mL) at −78° C. under N2 and the reaction was stirred for 15 min. A solution of benzyl [(1S)-2-hydroxy-1-methylethyl]carbamate (965 mg, 4.61 mmol) in dry CH2Cl2 (12.6 mL) was added dropwise by cannula and the mixture was stirred at −78° C. for 30 min. Triethylamine (1.34 g, 1.85 mL, 13.2 mmol) was added and the reaction was allowed to warm to room temperature and was stirred for 2 h. Water (15 mL) was added and the aqueous phase was separated and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were washed with saturated NaHCO3 and brine, then dried (MgSO4) and concentrated in vacuo to afford benzyl [(1S)-1-methyl-2-oxoethyl]carbamate as a colorless oil. Rf=0.75 (50% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3) δ 9.58 (s, 1H), 7.39-7.35 (m, 5H), 5.39 (br s, 1H), 5.15 (s, 2H), 4.33 (m, 1H), 1.40 (d, J=7.1 Hz, 3H). the mixture was stirred at −78° C. for 30 min was stirred for 2 h the aqueous phase was separated extracted with CH2Cl2 (3×15 mL) The combined organic extracts were washed with saturated NaHCO3 and brine dried (MgSO4) concentrated in vacuo

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

Procedure: Subsequently, to a solution of [(1S)-1-(hydroxymethyl)ethyl]carbamic acid benzyl ester (4.61 g, 22.0 mmol) in dimethylformamide (140 ml) were added t-butyldiphenylsilyl chloride (6.87 ml, 26.4 mmol) and imidazole (1.80 g, 26.4 mmol) in an ice bath. The resulting mixture was stirred at room temperature for 6 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)-2-(t-butyldiphenylsilyloxy)-1-methylethyl]carbamic acid benzyl ester (10.7 g, yield 100%) as a colorless oil. 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

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

Procedure: To a solution of L-alaninol (2.00 g, 26.6 mmol) in methylene chloride (60 ml) were added chloroformic acid benzyl ester (4.57 ml, 32.0 mmol) and triethylamine (4.48 ml, 32.0 mmol) in an ice bath. The mixture was stirred at room temperature overnight. 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)-2-hydroxy-1-methylethyl]carbamic acid benzyl ester (4.61 g, yield 83%) 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

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

Procedure: To a solution of L-alaninol (2.00 g, 26.6 mmol) in methylene chloride (60 ml) were added chloroformic acid benzyl ester (4.57 ml, 32.0 mmol) and triethylamine (4.48 ml, 32.0 mmol) in an ice bath. The mixture was stirred at room temperature overnight. 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)-2-hydroxy-1-methylethyl]carbamic acid benzyl ester (4.61 g, yield 83%) 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

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

Procedure: Dimethylsulfoxide (1.01 g, 918 μL, 12.9 mmol) was added dropwise to a stirred solution of oxalyl chloride (790 mg, 543 μL, 6.23 mmol) in dry CH2Cl2 (12.6 mL) at −78° C. under N2 and the reaction was stirred for 15 min. A solution of benzyl [(1S)-2-hydroxy-1-methylethyl]carbamate (965 mg, 4.61 mmol) in dry CH2Cl2 (12.6 mL) was added dropwise by cannula and the mixture was stirred at −78° C. for 30 min. Triethylamine (1.34 g, 1.85 mL, 13.2 mmol) was added and the reaction was allowed to warm to room temperature and was stirred for 2 h. Water (15 mL) was added and the aqueous phase was separated and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were washed with saturated NaHCO3 and brine, then dried (MgSO4) and concentrated in vacuo to afford benzyl [(1S)-1-methyl-2-oxoethyl]carbamate as a colorless oil. Rf=0.75 (50% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3) δ 9.58 (s, 1H), 7.39-7.35 (m, 5H), 5.39 (br s, 1H), 5.15 (s, 2H), 4.33 (m, 1H), 1.40 (d, J=7.1 Hz, 3H). the mixture was stirred at −78° C. for 30 min was stirred for 2 h the aqueous phase was separated extracted with CH2Cl2 (3×15 mL) The combined organic extracts were washed with saturated NaHCO3 and brine dried (MgSO4) concentrated in vacuo

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

Procedure: A procedure similar to that described in Preparation 8 was repeated, except that 7.00 g of (S)-2-benzyloxycarbonylaminopropanol (prepared as described in Preparation 31), 6.03 g of t-butyldimethylsilyl chloride, 5.45 g of imidazole and 100 ml of anhydrous dimethylformamide were used, to give 10.52 g of the title compound having an Rf value of 0.48 (on silica gel thin layer chromatography, using a 1:7 by volume mixture of ethyl acetate and hexane as the developing solvent). A procedure similar to that described in Preparation 8

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

Procedure: A procedure similar to that described in Preparation 7 was repeated, except that 14.55 g of L-alaninol, 126 ml of a 30-35% w/v solution of benzyloxycarbonyl chloride in toluene, 29.6 ml of triethylamine and 100 ml of anhydrous tetrahydrofuran were used, to give 8.15 g of the title compound, melting at 79° C. to 80° C. A procedure similar to that described in Preparation 7

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

Procedure: A procedure similar to that described in Preparation 8 was repeated, except that 7.00 g of (S)-2-benzyloxycarbonylaminopropanol (prepared as described in Preparation 31), 6.03 g of t-butyldimethylsilyl chloride, 5.45 g of imidazole and 100 ml of anhydrous dimethylformamide were used, to give 10.52 g of the title compound having an Rf value of 0.48 (on silica gel thin layer chromatography, using a 1:7 by volume mixture of ethyl acetate and hexane as the developing solvent). A procedure similar to that described in Preparation 8

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

Procedure: A procedure similar to that described in Preparation 7 was repeated, except that 14.55 g of L-alaninol, 126 ml of a 30-35% w/v solution of benzyloxycarbonyl chloride in toluene, 29.6 ml of triethylamine and 100 ml of anhydrous tetrahydrofuran were used, to give 8.15 g of the title compound, melting at 79° C. to 80° C. A procedure similar to that described in Preparation 7

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

Procedure: A solution of (S)-benzyl(1-hydroxypropan-2-yl)carbamate (400 g, 1.91 mol) and triethylamine (270 g, 2.67 mol) in methylene chloride (2.4 L) was cooled to 0° C. To this mixture was added methanesulfonyl chloride (263 g, 2.30 mol) at an internal temperature of 5° C. or below. Subsequently, the resulting reaction mixture was stirred at room temperature for 16 hours. After confirming the disappearance of the starting materials by TLC, to the reaction mixture was added purified water. The resulting organic layer was partitioned, washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give the target product as a yellow solid (519 g, yield 94.5%). Subsequently, the resulting reaction mixture to the reaction mixture was added purified water The resulting organic layer was partitioned washed with saturated brine dried over magnesium sulfate filtered The filtrate was concentrated under reduced pressure

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

Procedure: To a solution of (S)-(+)-2-amino-1-propanol (200 g, 2.66 mol) in purified water (400 mL) was added sodium bicarbonate (246 g, 2.93 mol). To this mixture was added benzyl chloroformate (500 g, 2.93 mol) in tetrahydrofuran (800 mL) at an internal temperature of 20° C. or below. Subsequently, the resulting reaction mixture was stirred at room temperature for 16 hours. After confirming the disappearance of the starting materials by TLC, the reaction mixture was then extracted with ethyl acetate. The organic layer was washed with 0.5 N hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous sodium sulfate. The resulting solution was filtered and concentrated under reduced pressure. The residue was crystallized from petroleum ether to give the target product as a white solid (403 g, yield 72.3%). Subsequently, the resulting reaction mixture the reaction mixture was then extracted with ethyl acetate The organic layer was washed with 0.5 N hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine dried over anhydrous sodium sulfate The resulting solution was filtered concentrated under reduced pressure The residue was crystallized from petroleum ether