反应详情

温度

-10 °C

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.

1. additionCharged slowly within 1 hour
2. temperaturemaintained the reaction mass at −10° C. to −5° C. for 3.5 to 4.5 hrs
3. customAfter completion of the reaction
4. stirringstirred for 15 minutes at 25-30° C
5. customSeparated the organic layer
6. additioncharged in the reaction flask
7. temperaturemaintained the reaction mixture at 25-30° C. for 1-2 hours
8. additionAfter completion of 2 hours charged DM water (330 ml)
9. stirringstirred for 20-25 minutes
10. customSeparated the organic layer
11. washwashed with DM water (330 ml)
12. temperaturecooled to 15-20° C.
13. extractionExtracted the aqueous layer with dichloromethane (1×550 ml, 2×330 ml)
14. washwashed with DM water
15. stirringstirred at 25-30° C. for 10-15minutes
16. waitCharcoalised dichloromethane layer at 25-30° C. for 30 minutes
17. filtrationfiltered
18. washwashed the hyflow bed with dichloromethane (2×110 ml)
19. concentrationConcentrated the filtrate under reduced pressure below 40° C.
20. customdegas under vacuum at 35-40° C. for 3-4hrs