121-88-0

619-10-3

General procedure for the synthesis of 2-chloro-5-nitrophenol from 2-amino-5-nitrophenol: In Preparation Example 14, 1-amino-5-nitrophenol (2 g, 12.97 mmol) and sodium nitrite (0.9 g, 12.97 mmol) were firstly dissolved in 10 ml of water and stirred well. Subsequently, 30 ml of 48% fluoboric acid (HBF4) was slowly added at room temperature with continuous stirring for 30 minutes. Next, copper (I) chloride (642 mg, 6.48 mmol) was added and the reaction mixture was heated to 80°C and maintained for 3 hours. After completion of the reaction, the mixture was poured into ice-cold water at 0°C and extracted with 200 ml of saturated sodium bicarbonate solution and 200 ml of ethyl acetate. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated in vacuum. Purification by column chromatography (hexane/ethyl acetate, 15/1) gave 2-chloro-5-nitrophenol (0.46 g, 23% yield). Referring to the exemplary method of synthesis 9, the target compound (0.167 g, 94% yield) was further reacted with 2-chloro-5-nitrophenol (0.36 g, 2.29 mmol).