N-(4-Methoxyphenyl)Acetamide → N-[3-(2-bromohexanoyl)-4-hydroxyphenyl]acetamide

Participants

Reaction Steps

Aluminium chloride (20.00 g, 150 mmol) was carefully added to a stirred solution of N-(4-methoxyphenyl)acetamide [3a] (8.26 g, 50.0 mmol) in dichloromethane (30 mL) at 0-5° C. (ice/water bath). Nitromethane (8.2 mL, 150 mmol) was added to the mixture in one portion. A solution of 2-bromohexanoyl chloride (12.81 g, 60.0 mmol) in dichloromethane (20 mL) was added dropwise to the stirred mixture at room temperature. The obtained mixture was stirred for 4 hours at the same temperature. Aluminum chloride (6.67 g, 50.0 mmol) was added in one portion to the stirred mixture at room temperature. The mixture was stirred overnight at the same temperature. The mixture was carefully poured into ice/water mixture. The mixture was extracted with ethyl acetate (150 mL then 2×50 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure at 50° C. (water bath). The residue (21.20 g) was stirred with hexane (150 mL) for 1 hour at room temperature. The precipitated solids were filtered off, washed on the filter with hexane and dried at 50° C. (water bath) to the constant weight to give 15.03 g (91.6%) of N-[3-(2-bromohexanoyl)-4-hydroxyphenyl]acetamide [6a] as yellow crystals with mp 137-138° C. (toluene).

Provenance & Evidence