Sodium Iodide → 6-Chloro-1,3-dihydroindol-2-one

Temperature

120 °C

A reactor is loaded with 131 g (0.57 mol) of 6-chloro-5-(2-chloro-ethyl)-1,3-dihydro-indol-2-one, 125 g (0.57 mol) of piperazinyl benzoisothiazole, 260 ml of dimethylsulfoxide, 26 ml of water and 4.3 g (0.0285 mols) of NaI. The reaction mixture is added with 103 g (0.969 mol) of Na2CO3, with stirring under nitrogen atmosphere. The resulting mixture is heated to about 115-125° C. in 1 h and kept at said temperature under stirring for approx. 1 hr 45 min, then cooled and slowly added in about 25 min with isopropyl alcohol (650 ml), at a temperature of about 110° C., then slowly cooled at 25° C. The filtrate and the precipitate are washed with isopropyl alcohol (2×130 ml) to obtain 310 g of 5-(2-(4-benzo[d]isothiazol-3-yl) piperazin-1-yl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one free base, as a crystalline solid. The resulting product is placed in a 3 L beaker with 1500 ml of purified water, and 150 ml of 32% HCl are dropped therein with stirring. The reaction mixture is kept under stirring for 10 min, filtered, washed with purified water (2×500), dried to give 260 g of 5-(2-(4-benzo[d]isothiazol-3-yl) piperazin-1-yl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one hydrochloride, as a crystalline solid.

1. stirringunder stirring for approx. 1 hr 45 min
2. temperaturecooled
3. temperatureslowly cooled at 25° C
4. washThe filtrate and the precipitate are washed with isopropyl alcohol (2×130 ml)

ORD record

ord-dedacb1746644728b4c69a8b9b6206b7

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07608711B2