Sodium Iodide → Ziprasidone

HRID 1724633Notes

Reaction equation

HRID 1724633 reaction equation
Cl[CH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[Cl:13])[NH:9][C:8](=[O:14])[CH2:7]2.[N:15]1([C:21]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[S:23][N:22]=2)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>[Br-].C([P+](CCCC)(CCCC)CCCC)CCC.O.C1CCCCC1>[CH:27]1[CH:28]=[CH:29][C:24]2[S:23][N:22]=[C:21]([N:15]3[CH2:16][CH2:17][N:18]([CH2:2][CH2:3][C:4]4[CH:5]=[C:6]5[CH2:7][C:8](=[O:14])[NH:9][C:10]5=[CH:11][C:12]=4[Cl:13])[CH2:19][CH2:20]3)[C:25]=2[CH:26]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 27721443-(1-Piperazinyl)-1,2-benzisothiazoleHCID 106094745-(2-Chloroethyl)-6-chlorooxindole

Product 1

HCID 60854ZiprasidoneYield 73.5%

Reagents, catalysts & solvents 3

HCID 76564Tetrabutylphosphonium bromideCatalystHCID 962WaterSolventHCID 8078CyclohexaneSolvent

Conditions

Temperature
98.5 °C

Procedure

Charged 5-(2-chloroethyl)-6-chloro oxindole (50 gm), 3-(1-piperazinyl)-1,2-benzisothiazole (47.5 gm) and cyclohexane (500 mL) into an autoclave. To this sodium carbonate (46 gm), sodium iodide (3.2 gm), tetra butyl phosphonium bromide (14.8 gm) was added and the reaction was maintained at a temperature of 95-102° C. and the pressure was kept at 2.5 kg/cm2 till the reaction was completed. The reaction mass was cooled to 30° C. and water (250 mL) was added. The resulting compound was filtered and washed with water (100 mL). The wet compound was further slurred in water (500 mL), filtered and washed with water (100 mL). To the water wet compound was added acetone (500 mL) and was stirred at room temperature for 2 hours and 30 minutes. The solid was filtered, washed with acetone (100 mL) and dried at a temperature of 60-65° C. to afford the Ziprasidone base (65.7 gm).

Workup

  1. temperatureThe reaction mass was cooled to 30° C.
  2. filtrationThe resulting compound was filtered
  3. washwashed with water (100 mL)
  4. filtrationfiltered
  5. washwashed with water (100 mL)
  6. additionTo the water wet compound was added acetone (500 mL)
  7. filtrationThe solid was filtered
  8. washwashed with acetone (100 mL)
  9. customdried at a temperature of 60-65° C.

Sources & evidence

ORD record
ord-4b1804fdeae144deb50b9132a5266ff5
Source dataset
uspto-grants-2009_02
Patent number
US07488729B2

Reaction notes

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