Hydrochloric Acid → 1-{4-[2-(Dimethylamino)ethoxy]phenyl}ethan-1-one

Participants

Reaction Steps

2-(Dimethylamino)ethyl chloride hydrochloride (3.49 g, 23.2 mmol, 1.1 eq.) was added to a solution of 4′-hydroxyacetophenone (3.00 g, 22.0 mmol, 1 eq.) in acetone (100 mL), followed by the addition of potassium carbonate (9.12 g, 66.0 mmol, 3 eq.). The reaction mixture was heated under reflux overnight, cooled, and filtered; and the filtrate was concentrated and water (50 mL) was added, forming a cloudy solution. Hydrochloric acid (0.1N, 20 mL) was added, and the resulting clear solution was extracted three times with ethyl acetate. The aqueous phase was made basic with aqueous sodium hydroxide, forming a cloudy mixture, which was extracted with ethyl acetate (5×50 mL), then the ethyl acetate layer dried over magnesium sulfate and the ethyl acetate evaporated to give 4′-[2-(dimethylamino)ethoxy]acetophenone (2.90 g) as a light yellow oil, with identity and purity verified by LC-MS. Bromine (1.62 g, 10.1 mmol, 1.4 eq.) was added dropwise to a solution of the 4′-[2-(dimethylamino)ethoxy]acetophenone (1.5 g, 7.24 mmol) in acetic acid (5 mL) and the reaction mixture stirred at 24° C. for 3 hours, giving a dark red solution. The reaction mixture was cooled, water (5 mL) was added, and the mixture was lyophilized overnight. The crude 2-bromo-4′-[2-(dimethylamino)ethoxy]acetophenone was purified by preparative HPLC, followed by lyophilization of the appropriate fractions, to give 2-bromo-4′-[2-(dimethylamino)ethoxy]acetophenone (0.7 g) as an off-white solid.

Provenance & Evidence