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Synthesis Example 22 Synthesis of 3-cyano-5-chloro-2-hydroxyacetophenone: 2-amino-4-chlorophenol (50 g, 0.35 mol) was dissolved in 500 ml of 2.5N hydrochloric acid solution. The resulting solution was cooled to 0°C, at which temperature 25.25 g (0.37 mol) of sodium nitrite dissolved in 50 ml of water was added slowly and dropwise. The reaction mixture was stirred at 0°C for 30 min and then a pre-cooled solution of 70 g (0.42 mol) of potassium iodide dissolved in 100 ml of water was slowly added. Subsequently, the reaction mixture was gradually warmed to room temperature and stirred continuously at this temperature overnight. Upon completion of the reaction, the reaction mixture was extracted with ethyl acetate and the solvent was removed by reduced pressure distillation after combining the organic phases to give 89.7 g of 4-chloro-2-iodophenol in 99% yield.

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