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. whilst stirring at 250 rpm under a nitrogen sweep. 1-Chloro-4-(2-chloroethyl)benzene (Method 4, Step A, 500 g, 2856 mmol) was charged dropwise via an addition funnel over 1 h to give a clear golden oil. During the addition significant off-gassing was observed and the internal temperature reached 93° C. The reaction was stirred for a further 2 h at 90 to 95° C. Water (500 mL) and chlorobenzene (1000 mL) were added. The internal temperature dropped to 74° C. during the addition. The mixture was stirred at 70 to 75° C. for 15 min and then the layers were allowed to separate. The lower organic product phase was removed, and the upper aqueous phase was extracted with chlorobenzene (2×500 mL) by stirring at 70 to 75° C. for 15 min. The combined organic phases were washed with water (2×500 mL) by stirring at 70 to 75° C. for 15 min. After removal of the aqueous, the chlorobenzene solution containing the title compound was stirred overnight under nitrogen at 50° C. (jacket). Next, the solvent was removed by distillation under reduced pressure and the residue was diluted with chlorobenzene (2500 mL). The resulting solution contained 0.03% water by Karl-Fischer titration.

1. customInto a 5-L jacketed reactor equipped with a chiller
2. stirringwhilst stirring at 250 rpm under a nitrogen sweep
3. customto give a clear golden oil
4. additionDuring the addition significant
5. customreached 93° C
6. stirringThe reaction was stirred for a further 2 h at 90 to 95° C
7. additionThe internal temperature dropped to 74° C. during the addition
8. stirringThe mixture was stirred at 70 to 75° C. for 15 min
9. customto separate
10. customThe lower organic product phase was removed
11. extractionthe upper aqueous phase was extracted with chlorobenzene (2×500 mL)
12. stirringby stirring at 70 to 75° C. for 15 min
13. washThe combined organic phases were washed with water (2×500 mL)
14. stirringby stirring at 70 to 75° C. for 15 min
15. customAfter removal of the aqueous, the chlorobenzene solution
16. additioncontaining the title compound
17. stirringwas stirred overnight under nitrogen at 50° C. (jacket)
18. customNext, the solvent was removed by distillation under reduced pressure
19. additionthe residue was diluted with chlorobenzene (2500 mL)

ORD record

ord-a588bfbeb36745089433dbdc00bd5ab3

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952197B2