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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence