Hydrochloric Acid → HCID 21070815, compound

Participants

Reaction Steps

Degassed ethyl acetate (75 ml) was added to 5.5 g (19.6 mmol) 2-(ethyl)(2-hydroxyphenyl)aminoethylcarbamic acid, 1,1-dimethylethyl ester (6). To this was added 50 ml of 3N HCl and the reaction was stirred at ambient temperature overnight. TLC analysis was done using 30% EtOAc/hexanes. The reaction mixture was tranferred to a separatory funnel and extracted with 2×40 ml 1N HCl. The pooled aqueous layers were placed on the rotary evaporator and the volatiles removed. Water was added (about 50 ml) and removed by rotary evaporation, 2 cycles. The resulting oil was frozen in dry ice and placed under vacuum, then allowed to warm naturally to remove all volatiles. The resulting crispy material (7) was used without further purification, and kept free of air and moisture. Dry pyridine (75 ml) was added to the isolate by cannula. The flask was swirled to dissolve the material. Acetic anhydride (1.2 eq.) was added via syringe and the reaction was stirred under argon at ambient temperature. TLC analysis was performed with 10% methanol/chloroform. At the completion of the reaction, the pyridine was removed by rotary evaporation and the residue treated with 100 ml of 10% NaOH by stirring overnight under argon. The reaction was adjusted to pH 9 with 1N HCl and extracted with 4×75 ml ethyl acetate. The combined organic layers were washed with water, then brine (once each), pre-dried with Na2SO4, then dried overnight with MgSO4. The solution was collected by filtration and the volatiles were removed by rotary evaporation. The material was purified by flash chromatography on silica: loaded with 5% methanol/chloroform; eluted with 150 ml each of 3.3, 6.6, and 9.9% solvent as above to give 3-(ethyl)(2-acetylaminoethyl)aminophenol (8). Yield was 4.2 g (96%).

Provenance & Evidence