Sodium Iodide → 4-(Iodomethyl)benzonitrile

Sodium iodide (99 mg, 0.660 mmol) and 4-(chloromethyl)benzonitrile (100 mg, 0.660 mmol) were dissolved in Acetone (Volume: 2.199 mL) and allowed to stir at room temperature for 4 hours. The resulting solid was filtered and the filtrate concentrated to obtain 4-(iodomethyl)benzonitrile (130 mg, 0.535 mmol, 81% yield) as an orange oil. It was taken directly to the next step without characterization and purification. N-benzyl-1-(1H-indole-2-carbonyl)-N-methylpiperidine-4-carboxamide (100 mg, 0.266 mmol) was dissolved in 1.0 mL of DMF and added to a suspension of sodium hydride (12.78 mg, 0.320 mmol) in 2.0 of DMF. The reaction was stirred at 80° C. for 10 minutes before adding 4-(iodomethyl)benzonitrile (129 mg, 0.533 mmol) dissolved in 2.0 mL of DMF. The reaction was allowed to stir overnight. After 18 hours, the reaction was cooled to room temperature before diluting with water and ethyl acetate. The organic phase was washed with water followed by saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated. The crude material was purified via column chromatography using 50% ethyl acetate/hexanes to 100% ethyl acetate. The purification provided product as a white solid. (Yield: 50 mg, white solid) 1H-NMR (400 MHz, DMSO-d6) 7.78-7.67, 7.66-7.57, 7.49, 7.43-7.01, 6.80-6.68, 5.65-5.51, 4.62, 4.54-3.83, 3.16-2.83, 2.75, 2.35-2.26, 1.80-1.24