Isopropanol → 4-[4-(4-Nitrophenyl)piperazin-1-yl]phenol

Participants

Reaction Steps

Under nitrogen, 420 g (2.36 mol) N-(4-Hydroxyphenyl)-piperazine, 520.6 g (3.30 mol) 1-chloro-4-nitrobenzene and 457.5 g (3.54 mol) N,N-Diisopropylethylamine (Hünig's Base) are suspended in 1260 ml N-Methylpyrrolidone and heated to 120°-125° C. The clear solution is stirred at 120°-125° C. and the reaction is followed by HPLC. After complete reaction (5-7 hours) the solution is cooled to 75°-80° C. and 6.3 liters of isopropanol are added over a period of about 30 minutes to the reaction mixture while keeping the temperature at 75°-80° C. (slight heating is necessary). Towards the end of the addition the product starts to precipitate (yellow crystals). The suspension is cooled to 20°-25° C. and stirred overnight at this temperature. Afterwards the suspension is cooled to −10° to −5° C. and stirred for 30 minutes. The product is filtered off, washed with 1.7 liters isopropanol, followed by 5×840 ml warm (35°-40° C.) water. The product is dried under vacuum at 50° C. (slight stream of nitrogen) to constant weight.

Provenance & Evidence