拉科酰胺EP杂质E（R异构体）

反应条件: temp:52.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a reaction flask charged (2S)-N-benzyl-2-bromo-3-hydroxypropanamide (80.0 gms) and sodium azide (30.23 gms) in N,N-dimethylformamide (480 ml), stirred and raised the temperature to 50-55° C. and maintained for 4-5 hours. Stopped heating and cooled the reaction mixture to 20-25° C., charged DM water (400 ml), adjusted pH of the reaction mixture to 9-9.5 using 5% NaHCO3 solution. Extracted the reaction mixture with ethyl acetate (1×800 ml, 2×280 ml) separated the organic layer and combined all ethyl acetate layers, washed with saturated ammonium chloride solution (2×240 ml). The ethyl acetate layer was taken for hydrogenation to 2 lit autoclave. Charged ethyl acetate layer and 5% Pd-C (6.85 gms) was added and closed the autoclave. Applied 3.8 kg Hydrogen pressure maintaining temperature at 25-30° C. and maintained the reaction mixture at 25-30° C. for 1.0 hour. After completion of the reaction released Hydrogen pressure and flushed the autoclave with Nitrogen gas. Filtered the reaction mass through hyflo bed and washed hyflo bed with ethyl acetate. Concentrated filtrate under reduced pressure at 30-35° C. till two volumes of ethyl acetate remains in the reaction mixture. Removed vacuum and cooled the reaction mass to 0-5° C. and maintained for 2.0 hours. The reaction mass was filtered and washed with cold ethyl acetate (2×40 ml). Dried the product (2R)-2-amino-N-benzyl-3-hydroxypropanamide under vacuum at 25-30° C. till constant weight. maintained for 4-5 hours Stopped heating cooled the reaction mixture to 20-25° C. Extracted the reaction mixture with ethyl acetate (1×800 ml, 2×280 ml) separated the organic layer washed with saturated ammonium chloride solution (2×240 ml) Charged ethyl acetate layer and 5% Pd-C (6.85 gms) was added closed the autoclave Applied 3.8 kg Hydrogen pressure maintaining temperature at 25-30° C. maintained the reaction mixture at 25-30° C. for 1.0 hour flushed the autoclave with Nitrogen gas Filtered the reaction mass through hyflo bed washed at 30-35° C. Removed vacuum cooled the reaction mass to 0-5° C. maintained for 2.0 hours The reaction mass was filtered washed with cold ethyl acetate (2×40 ml) Dried the product (2R)-2-amino-N-benzyl-3-hydroxypropanamide under vacuum at 25-30° C. till constant weight

反应条件: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In an autoclave charged (2R)-2-azido-N-benzyl-3-hydroxypropanamide (68.0 gms) in ethyl acetate (680 ml). Charged catalyst 5% Pd-C (6.85 gms) and closed the autoclave. Applied 3.8 kg Hydrogen pressure maintaining temperature at 25-30° C. and maintained the reaction mixture at 25-30° C. for 1.0 hour. After completion of the reaction, released Hydrogen pressure and flushed the autoclave with Nitrogen gas. Filtered the reaction mass through hyflo bed and washed hyflo bed with ethyl acetate. Concentrated filtrate under reduced pressure at 30-35° C. till two volumes of ethyl acetate remains in the reaction mixture. Removed vacuum and cooled the reaction mass to 0-5° C. and maintained for 2.0 hours. The reaction mass was filtered and washed with cold ethyl acetate (2×40 ml). Dried the product (2R)-2-amino-N-benzyl-3-hydroxypropanamide under vacuum at 25-30° C. till constant weight. After completion of the reaction flushed the autoclave with Nitrogen gas Filtered the reaction mass through hyflo bed washed at 30-35° C. Removed vacuum cooled the reaction mass to 0-5° C. maintained for 2.0 hours The reaction mass was filtered washed with cold ethyl acetate (2×40 ml) Dried the product (2R)-2-amino-N-benzyl-3-hydroxypropanamide under vacuum at 25-30° C. till constant weight

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

实验步骤: To a 250 mL three-neck round bottom flask, 9.65 g (0.0497 mol) (R)-2-amino-N-benzyl-3-hydroxypropionamide, 120 mL tetrahydrofuran, and 7.58 g (0.0749 mol) triethylamine were added in sequence, the mixture was stirred to obtain a solution. At a normal temperature, 6.01 g (0.0554 mol) ethyl chlorocarbonate was added. After the reaction was completed, the solvent was evaporated, and the residue was added with 100 mL water, and stirred uniformly. The solution was extracted with 50 mL×3 ethyl acetate, and the organic phases were combined and dried over anhydrous sodium sulfate. The solvent was evaporated, to obtain a white solid of 9.67 g (0.0363 mol). The molar yield was 73.04%. to obtain a solution the solvent was evaporated the residue was added with 100 mL water stirred uniformly The solution was extracted with 50 mL×3 ethyl acetate dried over anhydrous sodium sulfate The solvent was evaporated to obtain a white solid of 9.67 g (0.0363 mol)

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)

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

实验步骤: Acetic anhydride (4 grams) was added to the solution of (R)-2-amino-N-benzyl-3-hydroxypropanamide compound of formula-10 (6 grams) in dichloromethane (60 ml) at 10-15° C. The reaction mixture was stirred for 3 hours and reaction mixture quenched with water. Both the organic and aqueous layers were separated. The organic layer was washed with aqueous sodium bicarbonate solution followed by water. The organic layer was distilled off completely under reduced pressure to get the title compound. reaction mixture quenched with water Both the organic and aqueous layers were separated The organic layer was washed with aqueous sodium bicarbonate solution The organic layer was distilled off completely under reduced pressure