11-(Piperazin-1-yl)dibenzo[b,f][1,4]thiazepine

753475-15-9

5747-48-8

General procedure for the synthesis of 11-(1-piperazinyl)dibenzo[b,f][1,4]thiazepine from 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepine hydrochloride: a toluene solution of 11-chloro-dibenzo[b,f][1,4]thiazepine (1500 mL, 0.686 mol) was mixed with 1500 mL of deionized water and 90 mL of HCl (32% w/w) were mixed. The reaction mixture was heated to 70 °C and stirred for 45 min. Stirring was stopped and allowed to stand for 30 minutes for phase separation. The lower aqueous phase was separated, which contained the HCl salt of 11-piperazin-1-yl dibenzo[b,f][1,4]thiazepine. Subsequently, the aqueous phase was treated with 1000 mL of toluene and 99 g aqueous NaOH (47% w/w). The mixture was heated to 70 °C and stirred for 45 min. Stirring was stopped and allowed to stand for 30 min for phase separation. The lower aqueous phase was discarded, the upper organic phase was retained and 300 mL of deionized water was added to it. The mixture was stirred for 15 minutes and then allowed to stand for 30 minutes. The aqueous phase was discarded and the organic phase was again extracted with 300 mL of deionized water. Approximately 750 mL of toluene was removed by distillation and the concentrate was cooled to 60°C. 200 mL of methyl tertiary butyl ether (MTBE) was added. The mixture was cooled to room temperature and inoculated with Type A crystalline seed. Subsequently, the mixture was cooled to 10 °C and kept under slow stirring for 3 hours. The solid product was separated by filtration through a #3 sintered funnel. The solid was washed with 120 mL of MTBE at room temperature and finally dried under vacuum at 40 °C to give 175 g (86.4% yield) of crystalline product.HPLC analysis showed a product purity of 99.9% w/w.