Benzoyl chloride → Methyl 3-hydroxy-5-[(phenylcarbonyl)oxy]benzoate

Participants

Reaction Conditions

Reaction Steps

To a flask fitted with thermometer, condenser, overhead stirrer, pH probe and nitrogen line was added methyl-3,5-dihydroxybenzoate (1.0 eq), 325 mesh potassium carbonate (3.0 eq) and dimethylformamide (DMF) (4 vols) under a nitrogen atmosphere. The mixture was heated to 47° C. for 1 hour, then benzoyl chloride (1.0 eq) was added slowly drop-wise via syringe pump over approximately 2 hours. Further benzoyl chloride was added (0.1 eq) over 20 minutes via syringe pump. The reaction mixture was held for 1.5 hours, then water (10 vols) and iso-propyl acetate (6 vols) were added. The reaction mixture was agitated for 30 minutes and then the layers were separated. The aqueous layer was re-extracted with a further charge of iso-propyl acetate (6 vols). The batch was separated, and the combined organic layers were washed with saturated brine (6 vols), then with a solution of 0.1N hydrochloric acid/brine. The iso-propyl acetate was distilled to dryness on the rotary evaporator. Iso-propyl acetate (6 vols) was added, and distilled to dryness on the rotary evaporator. Toluene (6 vols) was added and distilled to dryness on the rotary evaporator. Toluene (3.5 vols) was added and the reaction slurried for 30 minutes. The solid was filtered off and dried at 20° C.-40° C. to give the desired product as a solid (corrected yield 72%).

Provenance & Evidence