Acetyl chloride → Mexiletine acetate

Participants

Reaction Conditions

Reaction Steps

Acetyl chloride (99 ml, 1.39 mol, 1.5 eq) was added to a stirred suspension of mexiletine hydrochloride (200 g, 0.927 mol), ethyl acetate (750 ml), and 5N sodium hydroxide (750 ml) over a period of 35 minutes while keeping the temperature at ≤10° C. After the addition was complete, the reaction was allowed to stir for 45 minutes at 15-20° C. The mixture was then added to water (1 1) and the ethyl acetate layer separated. The aqueous layer was washed with ethyl acetate (2×300 ml) and the combined ethyl acetate layers were washed with saturated aqueous sodium bicarbonate until the washings were no longer acidic. The ethyl acetate solution was then washed with brine, dried over MgSO4, and concentrated to give N-[2-(2,6-dimethylphenoxy)-1-methylethyl]-acetamide (197 g, 96% yield, mp 85-85.8° C.).

Provenance & Evidence