反応 #7692

反応方程式

hydrogen chloride

5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one

1-methyl-2-pyrrolidinone

→

5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1, 3-dihydro-2H-indol-2-one hydrochloride

溶媒

isopropanol

反応条件

後処理

1. 1
   その他To a 3-necked flask equipped with mechanical stirrer
2. 2
   温度the suspension was warmed up to 35–40° C. to dissolution
3. 3
   ろ過The product was collected by filtration on a Buchner funnel
4. 4
   洗浄The filter cake is rinsed twice with 10 mL of isopropanol at 20–25° C.
5. 5
   その他the damp cake transferred to a flask
6. 6
   その他equipped with magnetic stirrer and nitrogen inlet
7. 7
   workup.ADDITIONIsopropanol was added (30 mL)
8. 8
   workup.STIRRINGthe suspension stirred at 20–25° C. for about 2 h
9. 9
   ろ過The product was collected by filtration on a Buchner funnel
10. 10
    洗浄The filter cake is rinsed with 3×10 mL of isopropanol at 20–25° C.
11. 11
    その他transferred to a drying oven
12. 12
    その他dried in vacuo at 70–75° C. for 43 h

実験手順

To a 3-necked flask equipped with mechanical 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 1-methyl-2-pyrrolidinone (60 mL) under nitrogen and the suspension was warmed up to 35–40° C. to dissolution. The flask was cooled to about 25° C. A 20.5% anhydrous solution of hydrogen chloride in isopropanol (6.45 g) was added and the mixture was stirred at about 25° C. for about 3 h. The product was collected by filtration on a Buchner funnel. The filter cake is rinsed twice with 10 mL of isopropanol at 20–25° C. and the damp cake transferred to a flask equipped with magnetic stirrer and nitrogen inlet. Isopropanol was added (30 mL) and the suspension stirred at 20–25° C. for about 2 h. The product was collected by filtration on a Buchner funnel. The filter cake is rinsed with 3×10 mL of isopropanol at 20–25° C. and transferred to a drying oven and dried in vacuo at 70–75° C. for 43 h. This afforded 4.52 g of anhydrous ziprasidone hydrochloride. The material contained 3.1% and 0.26% of residual NMP and IPA, respectively as determined by NMR.

出典