4-hydroxy-2-Methylbenzonitrile

21883-13-6

14143-26-1

General procedure for the synthesis of 3-methyl-4-cyanophenol from 2-methyl-4-methoxybenzonitrile: 4-methoxy-2-methylbenzonitrile (1.5 g, 10.2 mmol) was added to dry dichloromethane (34 mL). Boron trifluoride-dimethyl sulfide complex (10.7 mL, 102 mmol) was slowly added to the reaction mixture over 5 min. The reaction mixture was stirred at room temperature for 16 hours. The reaction was quenched by the addition of water and stirring was continued for 15 minutes until the fuming stopped. The reaction mixture was diluted with ethyl acetate (~100 mL) and partitioned through a dispensing funnel. The aqueous layer was extracted twice with ethyl acetate and the combined organic extracts were washed twice with water and then with brine. The organic layer was separated, dried with magnesium sulfate, filtered and concentrated in vacuum to give a light pink solid (1.305 g, 96% yield in two steps). The phenol intermediate was mixed with dry DMF (1.7 mL) in a flask. Imidazole (1.67 g, 24.5 mmol) and TBS-Cl (1.77 g, 11.8 mmol) were added and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into ether and washed three times with water and then once with brine. The organic layer was separated, dried with magnesium sulfate, vacuum filtered and concentrated to give a clear red oil. After further removal of the solvent by vacuum pump, the obtained oil (2.41 g, 96% yield in two steps) was used directly for the next reaction without further purification.