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

Temperature

80 °C

Into a 5-L jacketed reactor equipped with a chiller, overhead stirring, an anchor impeller, a thermocouple, a glycol condenser, and a nitrogen inlet vented to a caustic scrubber, was charged 1-aminopropan-2-ol (1102 mL, 14.3 mol). The reactor contents were heated to 80° C. and 1-chloro-4-(2-chloroethyl)benzene (Method 4, Step A, 500 g, 2856 mmol) was slowly charged over 40 min. The temperature of the gold-colored reaction mixture reached 97° C. during the addition and 101° C. approximately 1 min after addition was complete. The mixture was then allowed to cool to 90 to 95° C. and stirring was continued at that temperature for 2 h. Water (500 mL) and toluene (1000 mL) were added and the mixture was stirred at 75 to 80° C. for 15 min. The layers were allowed to separate at 70 to 75° C. The organic phase was removed and the aqueous phase was extracted with toluene at 70 to 75° C. for 15 min (2×500 mL). The combined organic phases were washed with water at 70 to 75° C. for 15 min (2×500 mL) and stirred overnight under nitrogen at 50° C. The solution was concentrated by distillation at 60° C. (jacket) under reduced pressure, and the residue was diluted with toluene to a total volume of about 800 mL. This solution was distilled a second time at 65° C. (jacket) under reduced pressure and the residue was diluted with toluene to a total volume of about 400 mL. The water content of the solution was 0.03% by Karl Fisher titration.

1. customInto a 5-L jacketed reactor equipped with a chiller
2. additionafter addition
3. temperatureto cool to 90 to 95° C.
4. stirringstirring
5. stirringthe mixture was stirred at 75 to 80° C. for 15 min
6. customto separate at 70 to 75° C
7. customThe organic phase was removed
8. extractionthe aqueous phase was extracted with toluene at 70 to 75° C. for 15 min (2×500 mL)
9. washThe combined organic phases were washed with water at 70 to 75° C. for 15 min (2×500 mL)
10. stirringstirred overnight under nitrogen at 50° C
11. concentrationThe solution was concentrated by distillation at 60° C. (jacket) under reduced pressure
12. additionthe residue was diluted with toluene to a total volume of about 800 mL
13. distillationThis solution was distilled a second time at 65° C. (jacket) under reduced pressure
14. additionthe residue was diluted with toluene to a total volume of about 400 mL

ORD record

ord-c2e4f8441e7a45e4a68601d8e6281ad3

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952197B2