Sodium Carbonate → Ziprasidone

HRID 1724635Notes

Reaction equation

HRID 1724635 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Cl.[N:8]1([C:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[S:16][N:15]=2)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[Cl:23][C:24]1[CH:32]=[C:31]2[C:27]([CH2:28][C:29](=[O:33])[NH:30]2)=[CH:26][C:25]=1[CH2:34][CH2:35]Cl>O>[CH:20]1[CH:21]=[CH:22][C:17]2[S:16][N:15]=[C:14]([N:8]3[CH2:13][CH2:12][N:11]([CH2:35][CH2:34][C:25]4[CH:26]=[C:27]5[CH2:28][C:29](=[O:33])[NH:30][C:31]5=[CH:32][C:24]=4[Cl:23])[CH2:10][CH2:9]3)[C:18]=2[CH:19]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 106094745-(2-Chloroethyl)-6-chlorooxindoleHCID 115217113-(1-Piperazinyl)-1,2-benzisothiazole monohydrochloride

Product 1

HCID 60854Ziprasidone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium carbonate (56.3 g) and 500 mL of water were placed into a round bottom flask. Added was 50 g of 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride and 50 g of 6-Chloro-5-(2-Chloroethyl)oxindole. The reaction mixture was then refluxed for 15 hours. The reaction completion was monitored by TLC. The reaction mass was cooled to room temperature. The resulting compound was filtered and washed with 50 mL of water. The wet compound and 250 mL of acetone were placed into a flask and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered to give a solid cake, which was washed with 50 mL of acetone. The wet cake and 750 mL of methanol were placed into a flask, which was heated to 50° C., and 14 mL of methane sulfonic acid was added to the solution over 20 minutes. The resulting reaction mass was cooled to room temperature and was subjected to a filtration to give a solid compound, which was washed with methanol. The wet compound and 750 mL of water were placed into a flask, and then pH of the solution was adjusted to pH 9 with caustic lye. The reaction mixture was then stirred at room temperature for 1 hour and filtered. The filtered compound was washed with water and dried at 70° C. to give 65 g of crystalline form Ziprasidone base.

Workup

  1. additionAdded
  2. temperatureThe reaction mixture was then refluxed for 15 hours
  3. filtrationThe resulting compound was filtered
  4. washwashed with 50 mL of water
  5. customThe wet compound and 250 mL of acetone were placed into a flask
  6. filtrationThe reaction mixture was filtered
  7. customto give a solid cake, which
  8. washwas washed with 50 mL of acetone
  9. customThe wet cake and 750 mL of methanol were placed into a flask
  10. temperaturewhich was heated to 50° C.
  11. addition14 mL of methane sulfonic acid was added to the solution over 20 minutes
  12. customThe resulting reaction mass
  13. temperaturewas cooled to room temperature
  14. filtrationwas subjected to a filtration
  15. customto give a solid compound, which
  16. washwas washed with methanol
  17. customThe wet compound and 750 mL of water were placed into a flask
  18. stirringThe reaction mixture was then stirred at room temperature for 1 hour
  19. filtrationfiltered
  20. washThe filtered compound was washed with water
  21. customdried at 70° C.
  22. customto give 65 g

Sources & evidence

ORD record
ord-1d69d96ce68b45ed989cdce50c7667e2
Source dataset
uspto-grants-2009_02
Patent number
US07488729B2

Reaction notes

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