4-(4-(4-Nitrophenyl)-1-piperazinyl)phenol

56621-48-8

100-00-5

112559-81-6

Under nitrogen protection, 420 g (2.36 mol) of 4-(1-piperazinyl)phenol, 520.6 g (3.30 mol) of 4-chloronitrobenzene, and 457.5 g (3.54 mol) of N,N-diisopropylethylamine (Huenig's base) were suspended in 1260 mL of N-methylpyrrolidone. The mixture was heated to 120-125°C until a clarified solution was formed. This temperature was maintained and the progress of the reaction was monitored by HPLC. Upon completion of the reaction (5-7 hr), the reaction solution was cooled to 75-80°C. 6.3 L of isopropanol was slowly added to the reaction mixture over a period of about 30 min while maintaining the temperature at 75-80°C (with slight heating if necessary). At the end of the addition, the product began to precipitate as yellow crystals. The suspension was cooled to 20-25°C and stirred at this temperature overnight. Subsequently, the suspension is further cooled to -10 to -5°C and stirred for 30 minutes. The product was collected by filtration and washed sequentially with 1.7 L of isopropanol and 5 x 840 mL of warm water (35-40°C). Finally, the product was dried under vacuum at 50°C (accompanied by a slight stream of nitrogen) to constant weight. The yield was 96% and the purity as determined by HPLC was 93%, which corresponded to the standard.