General procedure for the synthesis of 3-chloro-4-hydroxybenzonitrile from 3-chloro-4-methoxybenzonitrile: To a solution of 3-chloro-4-methoxybenzonitrile (4.25 g) in dichloromethane (DCM, 85 mL) was added slowly and dropwise at -78 °C a dichloromethane solution (50.7 mL) of 1 M boron tribromide (BBr3). The reaction mixture was stirred at -78 °C for 10 min and then moved to room temperature to continue stirring overnight. Subsequently, the reaction mixture was heated to 40 °C and stirred for 4.5 days, during which time additional boron tribromide solution (26 mL) was added on the first, second and third days, respectively. Upon completion of the reaction, the reaction mixture was carefully quenched with water and the solid precipitate was collected by filtration. The aqueous and organic layers were separated, the aqueous layer was washed with dichloromethane and the organic phases were combined. The organic layer was dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (Büchi Sepacore system, 50 g silica gel column, solvent A: heptane, solvent B: ethyl acetate (EA), gradient elution (solvent B was increased from 0% to 40%) at a flow rate of 30 mL/min), yielding 3.17 g of brown oily product. Liquid chromatography-mass spectrometry (LC-MS) analysis (Condition A): retention time (tR) = 0.68 min; [M + H]+ peak was not detected.
