反应详情

温度

110 °C

40 g (0.392 mol) of N-(2-aminoethyl)acetamide and 59.4 g (0.587 mol) of triethylamine were dissolved in 600 ml of dichloromethane. The solution was cooled down to 0 . . . +5° C. after which 67.2 g (0.587 mol) of methanesulfonyl chloride was added during a period of 1-1.5 h under continuous stirring, while keeping the temperature not higher than +5° C. during the addition. When the addition was finished the reaction mixture was stirred for another 3 hours while the temperature was allowed to rise to room temperature. After the reaction was completed the reaction mixture was evaporated to dryness. Dichloromethane saturated with ammonia (2000 ml) was added to the evaporation residue and the mixture was triturated for 15-30 min at room temperature. The formed precipitate was filtered off and the filtrate was evaporated to dryness. The evaporation residue was dissolved in 6 M hydrochloric acid (980 ml). The solution was heated to reflux (approx. 110° C.) and stirred at this temperature for 2 h. When the reaction was finished the reaction mixture was allowed to cool down to 60° C. and then evaporated to dryness under reduced pressure. The evaporation residue was dissolved in 460 ml of methanol and then again evaporated to dryness to remove traces of water. The residue was dissolved in another 460 ml of methanol after which 3 g of −activated carbon (Norit® SX1) was added. The mixture was stirred for 15 min at 30° C., and filtered. The methanol solution was concentrated to about one third of the original mass. The crystallization was initiated by adding 85 ml of dichloromethane during 1 h under constant stirring. The solution was seeded by adding approximately 200 mg of seeding material N-(2-aminoethyl)methanesulfonamide hydrochloride. The solution was stirred for 15 min after which slow dichloromethane addition (1600 ml) was continued over a period of 6 hours under constant stirring. The mixture was cooled to 5° C. and stirred at this temperature for another 3 hours. The crystals were filtered and washed with 2×70 ml of cold acetone. The product was dried under vacuum at 30° C. overnight. The yield was typically in the range of 70-80%.

1. temperatureThe solution was cooled down to 0
2. customhigher than +5° C.
3. additionduring the addition
4. additionWhen the addition
5. customto rise to room temperature
6. customwas evaporated to dryness
7. additionDichloromethane saturated with ammonia (2000 ml) was added to the evaporation residue
8. customthe mixture was triturated for 15-30 min at room temperature
9. filtrationThe formed precipitate was filtered off
10. customthe filtrate was evaporated to dryness
11. dissolutionThe evaporation residue was dissolved in 6 M hydrochloric acid (980 ml)
12. temperatureThe solution was heated
13. stirringstirred at this temperature for 2 h
14. temperatureto cool down to 60° C.
15. customevaporated to dryness under reduced pressure
16. dissolutionThe evaporation residue was dissolved in 460 ml of methanol
17. customagain evaporated to dryness
18. customto remove traces of water
19. dissolutionThe residue was dissolved in another 460 ml of methanol after which 3 g of −activated carbon (Norit® SX1)
20. additionwas added
21. stirringThe mixture was stirred for 15 min at 30° C.
22. filtrationfiltered
23. concentrationThe methanol solution was concentrated to about one third of the original mass
24. customThe crystallization
25. additionby adding 85 ml of dichloromethane during 1 h under constant stirring
26. additionby adding approximately 200 mg of seeding material N-(2-aminoethyl)methanesulfonamide hydrochloride
27. stirringThe solution was stirred for 15 min
28. additionafter which slow dichloromethane addition (1600 ml)
29. waitwas continued over a period of 6 hours under constant stirring
30. temperatureThe mixture was cooled to 5° C.
31. stirringstirred at this temperature for another 3 hours
32. filtrationThe crystals were filtered
33. washwashed with 2×70 ml of cold acetone
34. customThe product was dried under vacuum at 30° C. overnight