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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)

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 12.54 g of (R)-2-benzyloxycarbonylaminopropanol (prepared as described in Preparation 23), 9.97 g of t-butyldimethylsilyl chloride, 4.90 g of imidazole and 150 ml of anhydrous dimethylformamide were used, to give 16.43 g of the title compound having an Rf value of 0.54 (on silica gel thin layer chromatography, using a 1:4 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: 11.42 g of benzyloxycarbonyl chloride were added dropwise to a mixture of 5.00 g of D-alaninol, 18.49 g of potassium carbonate, 15 ml of ethyl acetate and 15 ml of water, and the mixture was stirred at room temperature for 1.5 hours. At the end of this time, the ethyl acetate layer was separated, and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layer and the extract were combined, dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The crude crystals which precipitated were collected by filtration and washed with hexane, to give 13.68 g of the title compound, melting at 78° C. to 80° C. At the end of this time, the ethyl acetate layer was separated the aqueous layer was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated by evaporation under reduced pressure The crude crystals which precipitated were collected by filtration washed with hexane

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

Procedure: To a solution of benzyl [(1R)-2-hydroxy-1-methylethyl]carbamate (0.5 g, 2.38 mmol) in acetonitrile (20 mL), silver oxide (3.8 g, 13.09 mmol) is added followed by the addition of methyl iodide (1.94 mL, 23.8 mmol). The resultant mixture was stirred overnight at room temperature. The insoluble salt was filtered off and the filtrate was concentrated. The residue was flashed using silica and Ethyl acetate/hexanes system as eluent to give the desired product as clear oil (0.38 g). The insoluble salt was filtered off the filtrate was concentrated

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

Procedure: 11.42 g of benzyloxycarbonyl chloride were added dropwise to a mixture of 5.00 g of D-alaninol, 18.49 g of potassium carbonate, 15 ml of ethyl acetate and 15 ml of water, and the mixture was stirred at room temperature for 1.5 hours. At the end of this time, the ethyl acetate layer was separated, and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layer and the extract were combined, dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The crude crystals which precipitated were collected by filtration and washed with hexane, to give 13.68 g of the title compound, melting at 78° C. to 80° C. At the end of this time, the ethyl acetate layer was separated the aqueous layer was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated by evaporation under reduced pressure The crude crystals which precipitated were collected by filtration washed with hexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triphenylphospine (24 g, 91.8 mmol) was added to a solution of imidazole (12.5 g, 184 mmol) in CH2Cl2 (231 ml), then was cooled to 0 degrees C. Iodine (23.3 g, 91.8 mmol) was added to the suspension. The reaction mixture turned yellow, then faintly brown. After 5 minutes ((R)-2-hydroxy-1-methyl-ethyl)-carbamic acid benzyl ester (9.59 g, 45.9 mmol) was added and the reaction mixture was warmed to RT then stirred for 3 h. Then, H2O (7 ml) was added and the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml). The aqueous layer was extracted again with CH2Cl2 (200 ml). The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3: H2O (140 ml), then brine (400 ml). The combined organics were dried with MgSO4, filtered, concentrated in vacuo, then filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter). The solution was concentrated in vacuo, then the solid was washed with hexane and the resultant white solid was used in the next reaction without further purification (11 g, 75%). the reaction mixture was warmed to RT the reaction mixture was partitioned between CH2Cl2 (300 ml) and H2O (600 ml) The aqueous layer was extracted again with CH2Cl2 (200 ml) The combined organic layer was then washed with a solution of 1:9 aq. saturated Na2S2O3 The combined organics were dried with MgSO4 filtered concentrated in vacuo filtered through a plug of silica gel washing with 15% EtOAc/hexanes (1.5 liter) The solution was concentrated in vacuo the solid was washed with hexane the resultant white solid was used in the next reaction without further purification (11 g, 75%)