1-Amino-2-propanol → 1-((4-Chlorophenethyl)amino)propan-2-ol

Temperature

84 °C

Into a 4-L jacketed reactor, equipped with an overhead stirrer, a thermocouple, a condenser and a nitrogen inlet was charged 1-amino-2-propanol (1094 mL, 14.2 mol). Stirring was commenced and the reactor jacket was heated to 95° C. (84° C. internal temperature). 1-Chloro-4-(2-chloroethyl)benzene (˜496 g, 2.833 mol) (501 g of the mixture containing N,N-dimethylformamide from Step A) was added dropwise over ˜80 min at an internal temperature of 84 to 99° C. On completion of the addition the reaction was stirred at 90 to 95° C. for 2 h and then cooled to 85° C. Water (500 mL) and toluene (1 L) were added while maintaining the internal temperature at 70 to 75° C. Stirring was continued at that temperature for another 15 min and then stirring was discontinued and the phases were allowed to separate at 70 to 75° C. The aqueous phase was extracted with toluene (2×500 mL) at 70 to 75° C. The organic phases were combined, cooled to 50° C. and stirred at that temperature overnight. The solution was then heated to 60° C., washed with water (500 mL) and concentrated under reduced pressure at 58 to 65° C. After approximately 650 mL of distillate had been removed, fresh toluene (650 mL) was added. The water content of the resulting solution was determined to be 0.0854% by Karl Fischer titration and the solution was immediately carried forward to Step C.

1. customInto a 4-L jacketed reactor, equipped with an overhead stirrer
2. additionwas added dropwise over ˜80 min at an internal temperature of 84 to 99° C
3. additionOn completion of the addition the reaction
4. stirringwas stirred at 90 to 95° C. for 2 h
5. temperaturecooled to 85° C
6. temperaturewhile maintaining the internal temperature at 70 to 75° C
7. stirringStirring
8. stirringstirring
9. customto separate at 70 to 75° C
10. extractionThe aqueous phase was extracted with toluene (2×500 mL) at 70 to 75° C
11. temperaturecooled to 50° C.
12. stirringstirred at that temperature overnight
13. temperatureThe solution was then heated to 60° C.
14. washwashed with water (500 mL)
15. concentrationconcentrated under reduced pressure at 58 to 65° C
16. customAfter approximately 650 mL of distillate had been removed
17. additionfresh toluene (650 mL) was added

ORD record

ord-4e9f4ed60c864be4aa75253ab968e7b4

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952197B2