Hydrochloric Acid → Ziprasidone Hydrochloride

Participants

Reaction Steps

To a flask equipped with magnetic stirrer, thermometer and nitrogen inlet was added 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one free base (5.0 g) and ethanol (100 mL) and the suspension was stirred at 20–25° C. under nitrogen. A 20.5% anhydrous solution of hydrogen chloride in isopropanol (6.45 g) was added and the mixture was stirred for about 24 h. The product was collected by filtration on a Buchner funnel. The filter cake is rinsed with 3×10 mL of ethanol at 20–25° C. and transferred to a drying oven and dried in vacuo at 65–70° C. for about 24 h., then at 70–75° C. for another 24 h. This afforded 5.27 g of anhydrous ziprasidone hydrochloride. The material contained a small amount of residual ethanol, 0.7% determined by NMR. The IR and powder X-ray diffractogram matched that of the desired anhydrous product as depicted in U.S. Pat. No. 5,312,925.

Provenance & Evidence