4-Phenylmethoxy-3-methoxyphenylacetonitrile was prepared by reaction of 4-hydroxy-3-methoxyphenylacetonitrile (1.08 g, 6.60 mmol, 1.0 eq.) and benzyl bromide (1.24 g, 7.26 mmol, 1.1 eq.) in acetone (14 mL) according to the modified method of Imbri et al. First, K2CO3 (1.10 g, 7.92 mmol, 1.2 eq.) was added to the acetone solution of 4-hydroxy-3-methoxyphenylacetonitrile and the suspension was stirred for 10 min. Subsequently, benzyl bromide was added slowly dropwise via syringe. The reaction mixture was heated to reflux for 4 hours. Upon completion of the reaction, the suspension was separated by filtration and the precipitated solid was washed with acetone (10 mL). The filtrate was concentrated under reduced pressure and diluted with dichloromethane (DCM, 50 mL). The organic layer was washed sequentially with 2N NaOH (30 mL) and brine (30 mL) and then dried with Na2SO4. Finally, the solvent was removed by vacuum to afford the target product, 4-phenylmethoxy-3-methoxyphenylacetonitrile, as a yellow solid (1.67 g, 6.59 mmol, quantitative yield). The thin layer chromatography (TLC) Rf value of the product was 0.43 (cyclohexane/ethyl acetate, 2:1). The melting point was 65-66 °C. Nuclear magnetic resonance hydrogen (1H NMR, 400 MHz, CDCl3) and carbon (13C NMR, 100.6 MHz, CDCl3) data were consistent with the literature reports, confirming the structure of the product.
