GENERAL STEPS: A solution of 4-fluorophenylmagnesium bromide was prepared by reacting 153.33 g (0.876 mol) of 4-fluorobenzene bromide, 25.33 g (1.055 mol) of magnesium scrapings and 0.05 g of iodine in 300 mL of anhydrous tetrahydrofuran. This Grignard reagent solution was slowly added to a suspension of 100 g (0.628 mol) 5-cyanophthalide. The reaction was carried out in 1000 mL of dichloromethane and the temperature was maintained at -6 to -2°C. Upon completion of the reaction, post-processing was carried out as in Example 1 to give a thick semi-solid product. This semi-solid was ground with 500 mL of isopropanol (IPA) and cooled at 0-5 °C to give the solid product 5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran (2b). The solid was collected by filtration and washed with cold 50 mL IPA. The yield of the product was 130-140 g and the HPLC purity was 99.32%.
