Ethylamine → 3-sulfopropylethylamino

Temperature

5 °C

Tetrahydrofuran (THF, 800 mL) was placed a 3 neck 2-L flask (equipped with a condenser) and cooled to 5° C. with an ice-bath. To the cold THF was added aqueous ethylamine (70 wt. % solution in water, 85 mL, 1.07 mol), followed by addition of a cold solution of 1,3-propane sultone (25.08 g, 201 mmol) in THF (100 mL) over 24-min period. The mixture was stirred, while cooled with an ice-bath, for 1 h. The ice-bath was removed and the mixture was stirred at room temperature overnight. It was then heated under reflux for 1 h to distill off the ethylamine. The hot mixture was biphasic. Upon cooling, a solid crystallized at the bottom of the flask. Ether (400 mL) was added and the mixture was cooled to −20° C. The supernatant was decanted. Methanol (about 120 mL) was added to the residue. The mixture was heated to reflux; and complete dissolution of the solid material was achieved. After the solution was cooled to room temperature, precipitates formed. The mixture was cooled in an ice-bath; and the solid material was collected by filtration, rinsed with cold methanol and dried in vacuo (20.66 g, pure by NMR analysis). The solid material was recrystallized from methanol (100 mL). After the mixture was cooled using an ice-bath, the solid was collected by filtration, rinsed with cold methanol, and dried in a vacuum oven at 40° C. Compound CV was obtained as white fine needles (19.12 g, 57%). The 1H and 13C NMR were consistent with the structure.

1. temperaturewhile cooled with an ice-bath, for 1 h
2. customThe ice-bath was removed
3. stirringthe mixture was stirred at room temperature overnight
4. temperatureIt was then heated
5. temperatureunder reflux for 1 h
6. distillationto distill off the ethylamine
7. temperatureUpon cooling
8. customa solid crystallized at the bottom of the flask
9. additionEther (400 mL) was added
10. temperaturethe mixture was cooled to −20° C
11. customThe supernatant was decanted
12. additionMethanol (about 120 mL) was added to the residue
13. temperatureThe mixture was heated to reflux
14. dissolutionand complete dissolution of the solid material
15. temperatureAfter the solution was cooled to room temperature
16. customprecipitates
17. customformed
18. temperatureThe mixture was cooled in an ice-bath
19. filtrationand the solid material was collected by filtration
20. washrinsed with cold methanol
21. customdried in vacuo (20.66 g, pure by NMR analysis)
22. customThe solid material was recrystallized from methanol (100 mL)
23. temperatureAfter the mixture was cooled
24. filtrationthe solid was collected by filtration
25. washrinsed with cold methanol
26. customdried in a vacuum oven at 40° C

ORD record

ord-810506e045bc4436b5943f253046d1f3

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642801B2