Phenetole → (5-Bromo-2-chlorophenyl)(4-ethoxyphenyl)methanone

Participants

Reaction Steps

To 5-bromo-2-chlorobenzoic acid (1500 g, 6.41 mol) and oxalyl chloride (975 g, 7.69 mol) in DCM (2.8 L) was added DMF (9 mL). Once the vigorous evolution of gas ceased, the reaction was stirred for 10 hours at RT. The solution was concentrated under vacuum to give a yellow residue. The residue was dissolved in DCM (1.2 L), then the stirred mixture was cooled to −3° C., and phenetole (799 g, 6.54 mol) was added. After the addition was complete, aluminum (III) chloride (973 g, 6.54 mol) was added over 1 hour while maintaining the reaction temperature below 4° C. The mixture was poured over 10 kg ice and stirred at 4° C. for 1 hour. The suspension was diluted with water (3 L) and extracted with DCM (10 L×2). The combined organic layers were washed with 1 N HCl (7.5 L×2), water (10 L), 1N sodium hydroxide (7.5 L×2), and brine (10 L×2), and dried over sodium sulfate (1000 g). After removal of the volatiles, the residues were recrystallized from absolute ethanol (3.5 L) to give compound 2 as a white solid (1450 g, 67% yield, HPLC purity>99%).

Provenance & Evidence