2-Amino-5-chloro-2,6-difluorobenzophenone (1aa) (2.6 g, 9.7 mmol) was used as a raw material, which was dissolved in acetic acid (10 mL) and concentrated hydrochloric acid (4 mL), and the solution was cooled to 0 °C. A solution of sodium nitrite (NaNO2) (0.7 g, 10.7 mmol) in water (6 mL) was added dropwise while maintaining the temperature at 0-5 °C. After addition, the reaction mixture was stirred at 0 °C for 30 min. Subsequently, cold ethyl acetate (EtOAc) (20 mL) was added dropwise and the solution was stirred for 20 minutes. Next, a solution of iodine (I2) (1.5 g, 5.8 mmol) and potassium iodide (KI) (1.9 g, 11.6 mmol) in water (10 mL) was added drop-wise, and the mixture was slowly warmed to room temperature and stirred for 1 hour. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate (200 mL) and washed with saturated sodium thiosulfate (Na2S2O3) aqueous solution (4 x 100 mL). The combined aqueous phases were back-extracted with ethyl acetate (3 x 50 mL). All organic phases were combined and washed sequentially with saturated sodium bicarbonate (NaHCO3) aqueous solution (3×50 mL), water (2×50 mL), dried with anhydrous sodium sulfate (Na2SO4), filtered, and concentrated under reduced pressure to afford the target product (5-chloro-2-iodophenyl)(2,6-difluorophenyl)methanone (2aa) (3.3 g, 90% yield) as a light yellow solid.
