(R)-(1-(苄基氨基)-3-羟基-1-氧代丙-2-基)氨基甲酸叔丁酯

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3.2 g (0.01 mol) of Intermediate 4 in 50 mL of toluene was added 0.61 g of tetrabutylammonium bromide and 5 ml of water. The resulting mixture was cooled to 10° C. and a solution of 2.4 g of sodium hydroxide in 2.5 ml of water was added dropwise maintaining the temperature below 10° C. Then, 5.54 g of dimethylsulfate was added dropwise maintaining the temperature below 10° C. After stirring at 10° C. for 2 hours, water (80 mL) was added and the reaction stirred at room temperature overnight. The layers were separated and the aqueous layer was washed twice with dichloromethane (50 mL). The combined organic phase was washed with sodium bicarbonate solution (2×30 mL) and brine. The solvent was removed under vacuum yielding 3.36 g of a pale red-oil. The oil was not purified and used directly in the following step. maintaining the temperature below 10° C maintaining the temperature below 10° C the reaction stirred at room temperature overnight The layers were separated the aqueous layer was washed twice with dichloromethane (50 mL) The combined organic phase was washed with sodium bicarbonate solution (2×30 mL) and brine The solvent was removed under vacuum

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

实验步骤: A solution of 12.86 g of Intermediate 3 and 0.65 g of p-toluensulfonic acid in 100 mL of ethanol was heated at reflux temperature for 2 hours. The solvent was evaporated under vacuum and to the residue was added ethyl acetate (100 mL) which resulted in the precipitation of a white solid. The solvent was partially distilled and 150 mL of petroleum oil was added and stirred overnight. The solid was collected by filtration and dried yielding 6.5 g of the title compound as a white solid. at reflux temperature for 2 hours The solvent was evaporated under vacuum and to the residue was added ethyl acetate (100 mL) which resulted in the precipitation of a white solid The solvent was partially distilled 150 mL of petroleum oil was added The solid was collected by filtration dried

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a reaction flask charged tert-butyl [(1R)-2-(benzylamino)-1-(hydroxymethyl)-2-oxoethyl]carbamate (110.0 gms) and tetrabutylammonium bromide (18.07 gms) in solvent dichloromethane (550 ml), stirred and cooled to −10° C. Charged aqueous solution of sodium hydroxide (75.0 gms in 195 ml of DM water) maintaining temperature at −10° C. to −5° C. Charged slowly within 1 hour, dimethyl sulfate (141.4 gms) maintaining temperature at −10° C. to −5° C. and maintained the reaction mass at −10° C. to −5° C. for 3.5 to 4.5 hrs. After completion of the reaction, charged DM water (550 ml) and stirred for 15 minutes at 25-30° C. Separated the organic layer and charged in the reaction flask. Charged conc. Hydrochloric acid (440 ml) within 15 min and maintained the reaction mixture at 25-30° C. for 1-2 hours. After completion of 2 hours charged DM water (330 ml) and stirred for 20-25 minutes. Separated the organic layer and washed with DM water (330 ml). Combined both aqueous layers and cooled to 15-20° C. to adjust pH of the solution to 13-14 with the help of 50% sodium hydroxide solution. Extracted the aqueous layer with dichloromethane (1×550 ml, 2×330 ml). Combined all dichloromethane layers and washed with DM water and stirred at 25-30° C. for 10-15minutes. Charcoalised dichloromethane layer at 25-30° C. for 30 minutes, filtered and washed the hyflow bed with dichloromethane (2×110 ml). Concentrated the filtrate under reduced pressure below 40° C. and degas under vacuum at 35-40° C. for 3-4hrs to get oily mass of (2R)-2-Amino-N-benzyl-3-methoxypropanamide. Charged slowly within 1 hour maintained the reaction mass at −10° C. to −5° C. for 3.5 to 4.5 hrs After completion of the reaction stirred for 15 minutes at 25-30° C Separated the organic layer charged in the reaction flask maintained the reaction mixture at 25-30° C. for 1-2 hours After completion of 2 hours charged DM water (330 ml) stirred for 20-25 minutes Separated the organic layer washed with DM water (330 ml) cooled to 15-20° C. Extracted the aqueous layer with dichloromethane (1×550 ml, 2×330 ml) washed with DM water stirred at 25-30° C. for 10-15minutes Charcoalised dichloromethane layer at 25-30° C. for 30 minutes filtered washed the hyflow bed with dichloromethane (2×110 ml) Concentrated the filtrate under reduced pressure below 40° C. degas under vacuum at 35-40° C. for 3-4hrs

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Accordingly to a solution of the compound tert-butyl [(R)-2-(benzylamino)-1-(hydroxymethyl)-2-oxoethyl]carbamate of Formula-XXI in dichloromethane, charged the phase transfer catalyst and cooled the reaction mass to −10° C. and charged dilute solution of sodium hydroxide. Maintaining the temperature at −10° C.-0° C. charged dimethyl sulfate and maintained the reaction under stirring for 3-5 hours. Charged water at the end of the reaction, stirred, separated the organic layer and extracted the aqueous layer with the dichloromethane. Combined the organic layer and acidified with concentrated hydrochloric acid. Charged water to the clear solution and stirred. Separated the aqueous layer and extracted the organic layer further with water. Combined the entire aqueous layer and adjusted the pH to 12 with aqueous sodium hydroxide solution. Extracted the aqueous layer with dichloromethane and separated the organic layer. Extracted the aqueous layer further with dichloromethane to ensure the complete extraction of the desired product. The organic layer is washed and concentrated to isolate the compound (2R)-2-amino-N-benzyl-3-methoxypropanamide of Formula-VIII. Maintaining the temperature at −10° C.-0° C. maintained the reaction stirred separated the organic layer extracted the aqueous layer with the dichloromethane Charged water to the clear solution and stirred Separated the aqueous layer extracted the organic layer further with water Extracted the aqueous layer with dichloromethane separated the organic layer Extracted the aqueous layer further with dichloromethane the complete extraction of the desired product The organic layer is washed concentrated

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3.2 g (0.01 mol) of Intermediate 4 in 50 mL of toluene was added 0.61 g of tetrabutylammonium bromide and 5 ml of water. The resulting mixture was cooled to 10° C. and a solution of 2.4 g of sodium hydroxide in 2.5 ml of water was added dropwise maintaining the temperature below 10° C. Then, 5.54 g of dimethylsulfate was added dropwise maintaining the temperature below 10° C. After stirring at 10° C. for 2 hours, water (80 mL) was added and the reaction stirred at room temperature overnight. The layers were separated and the aqueous layer was washed twice with dichloromethane (50 mL). The combined organic phase was washed with sodium bicarbonate solution (2×30 mL) and brine. The solvent was removed under vacuum yielding 3.36 g of a pale red-oil. The oil was not purified and used directly in the following step. maintaining the temperature below 10° C maintaining the temperature below 10° C the reaction stirred at room temperature overnight The layers were separated the aqueous layer was washed twice with dichloromethane (50 mL) The combined organic phase was washed with sodium bicarbonate solution (2×30 mL) and brine The solvent was removed under vacuum

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

实验步骤: A solution of 12.86 g of Intermediate 3 and 0.65 g of p-toluensulfonic acid in 100 mL of ethanol was heated at reflux temperature for 2 hours. The solvent was evaporated under vacuum and to the residue was added ethyl acetate (100 mL) which resulted in the precipitation of a white solid. The solvent was partially distilled and 150 mL of petroleum oil was added and stirred overnight. The solid was collected by filtration and dried yielding 6.5 g of the title compound as a white solid. at reflux temperature for 2 hours The solvent was evaporated under vacuum and to the residue was added ethyl acetate (100 mL) which resulted in the precipitation of a white solid The solvent was partially distilled 150 mL of petroleum oil was added The solid was collected by filtration dried

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

实验步骤: To a 500 mL four-neck round bottom flask, 34.0 g (R)-N-benzyl-2-(tert-butoxycarbonylamino)-3-hydroxypropionamide and 350 mL dichloromethane were added, and the mixture was stirred to obtain a clear solution. At 20-25° C., 40.0 g concentrated hydrochloric acid (having a mass concentration of 36.0%) was added, and the reaction was continued. TLC tracking was performed, till the raw materials were completely converted. After the reaction was completed, the temperature was decreased to 20° C. The mixture was suction-filtered, to obtain a white needle-like crystal. The obtained white crystalline solid was dissolved in 50 g water. At 20-25° C., 30% sodium hydroxide solution was added to adjust the pH value of the system to 8-9. After the addition, the solution was stirred continuously, and a white flaky crystal was precipitated. The mixture was suction-filtered, and the filter was washed and dried, to obtain a target product of 16.5 g (0.085 mol). The molar yield was 73.52%. to obtain a clear solution At 20-25° C. was added was decreased to 20° C The mixture was suction-filtered to obtain a white needle-like crystal After the addition the solution was stirred continuously a white flaky crystal was precipitated The mixture was suction-filtered the filter was washed dried to obtain a target product of 16.5 g (0.085 mol)