Anisole → (5-Bromo-2-methylphenyl)(4-methoxyphenyl)methanone

Participants

Reaction Steps

To a stirred suspension of Part A 5-bromo-2-methylbenzoic acid (43 g, 200 mmol) in 200 mL of CH2Cl2 containing oxalyl chloride (140 mL of a 2M CH2Cl2 solution) was added 0.25 mL of DMF. Once the vigorous evolution of gas ceased, the reaction was stirred 6 hr prior to removal of the volatiles using a rotary evaporator. After dissolving the crude 5-bromo-2-methylbenzoyl chloride in 150 ml of CS2, the resulting solution was cooled to 4° while stirring with an overhead stirrer prior to addition of anisole (21.6 g, 200 mmol) followed by AlCl3 (29.3 g, 220 mmol) in portions. The reaction, after warming to 20° over 1 hr, was stirred for 15 hr prior to quenching by pouring over ice/conc HCl. Subsequently, the suspension was diluted with 500 ml H2O and stirred until all solids were dissolved. The mixture was extracted 3× with EtOAc. The combined organic extracts were washed 1× with 1N HCl, H2O, aq NaHCO3, and brine prior to drying over Na2SO4. After removal of the volatiles, the resulting tan solid was recrystallized from 95% EtOH to yield 55 g of 5-bromo-2-methyl-4′-methoxybenzophenone.

Provenance & Evidence