Sodium Iodide → Ziprasidone

HRID 1796186Notes

Reaction equation

HRID 1796186 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.[S:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[N:16]1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>CC(CC(C)C)=O>[CH:22]1[CH:21]=[CH:20][C:19]2[S:15][N:16]=[C:17]([N:24]3[CH2:25][CH2:26][N:27]([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])[CH2:28][CH2:29]3)[C:18]=2[CH:23]=1

Participants

6

Reactant 4

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

Product 1

HCID 60854Ziprasidone

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

To a 125 mL round bottom flask equipped with an N2 inlet and condenser are added 0.73 g (3.2 mmol) 5-(2-chloroethyl)-6-chloro-oxindole, 0.70 g (3.2 mmol) N-(1,2-benzisothiazol-3-yl)piperazine, 0.68 g (6.4 mmol) sodium carbonate, 2 mg sodium iodide, and 30 mL methylisobutyl ketone. The reaction is refluxed for 40 hours, cooled, filtered, and evaporated. The residue is chromatographed on silica gel, eluting the by-products with ethyl acetate (1 L) and the product with 4% methanol in ethyl acetate (1.5 L). The product fractions (Rf=0.2 in 5% methanol in ethyl acetate) are evaporated, taken up in methylene chloride, and precipitated by addition of ether saturated with HCl; the solid is filtered and washed with ether, dried, and washed with acetone. The latter is done by slurrying the solid with acetone and filtering. Ziprasidone is obtained as a high melting, non-hygroscopic solid product having an expected melting point of 288° C. to 288.5° C.

Workup

  1. customTo a 125 mL round bottom flask equipped with an N2 inlet and condenser
  2. temperatureThe reaction is refluxed for 40 hours
  3. temperaturecooled
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue is chromatographed on silica gel
  7. washeluting the by-products with ethyl acetate (1 L)
  8. customThe product fractions (Rf=0.2 in 5% methanol in ethyl acetate) are evaporated
  9. customprecipitated by addition of ether saturated with HCl
  10. filtrationthe solid is filtered
  11. washwashed with ether
  12. customdried
  13. washwashed with acetone
  14. filtrationfiltering

Sources & evidence

ORD record
ord-5cf9374629e14c1a8a43cc1362aee2b5
Source dataset
uspto-grants-2006_04
Patent number
US07030142B1

Reaction notes

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