Saccharin → HCID 67809422, compound

Reaction equation

[H-].[Na+].[S:3]1([C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:7](=[O:8])[NH:6]1)(=[O:5])=[O:4].[Cl:15][C:16]1[CH:17]=[C:18]([N:26]2[CH2:31][CH2:30][N:29]([CH2:32][CH2:33]Cl)[CH2:28][CH2:27]2)[C:19]2[O:24][CH2:23][CH2:22][O:21][C:20]=2[CH:25]=1>CN(C=O)C>[ClH:15].[Cl:15][C:16]1[CH:17]=[C:18]([N:26]2[CH2:27][CH2:28][N:29]([CH2:32][CH2:33][N:6]3[C:7](=[O:8])[C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=4[S:3]3(=[O:4])=[O:5])[CH2:30][CH2:31]2)[C:19]2[O:24][CH2:23][CH2:22][O:21][C:20]=2[CH:25]=1

Participants

Procedure

To a stirred suspension of sodium hydride (0.31 g, 13 mmol) in 12 ml of dry DMF was added saccharin (2.29 g, 13 mmol) in 12 ml of dry DMF. Stirring was continued for 10 minutes before 1-(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-4-(2-chloroethyl)piperazine (4.12 g, 13 mmol) (which can be obtained as described in EP-A-0190472) in 20 ml of dry DMF was added. The reaction mixture was heated under a nitrogen atmosphere for 7 hours, cooled down and extracted with ethylacetate (3×100 ml). The combined organic layers were washed with 5% NaHCO3, brine, dried and the solvent was removed in vacuo. The crude product was purified by flash column chromatography (silicagel/acetone:hexane=1:3) and the so-obtained free base was converted to its hydrochloride salt. Yield 3.13 g, (50%), m.p. 267°-70° C.