Hydrochloric Acid → Ziprasidone Hydrochloride

HRID 7596

Reaction equation

HRID 7596 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][C:26]=3[Cl:27])[NH:23][C:22](=[O:28])[CH2:21]4)[CH2:12][CH2:11]2)=[N:2]1.CN1CCCC1=O.Cl>C(O)(C)C>[ClH:27].[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][C:26]=3[Cl:27])[NH:23][C:22](=[O:28])[CH2:21]4)[CH2:14][CH2:15]2)=[N:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 60854Ziprasidone

Product 1

HCID 219099Ziprasidone Hydrochloride

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
25 °C

Procedure

To a 3-necked flask equipped with mechanical stirrer, thermometer and nitrogen inlet was added 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one free base (5.0 g) and 1-methyl-2-pyrrolidinone (60 mL) under nitrogen and the suspension was warmed up to 35–40° C. to dissolution. The flask was cooled to about 25° C. A 20.5% anhydrous solution of hydrogen chloride in isopropanol (6.45 g) was added and the mixture was stirred at about 25° C. for about 3 h. The product was collected by filtration on a Buchner funnel. The filter cake is rinsed twice with 10 mL of isopropanol at 20–25° C. and the damp cake transferred to a flask equipped with magnetic stirrer and nitrogen inlet. Isopropanol was added (30 mL) and the suspension stirred at 20–25° C. for about 2 h. The product was collected by filtration on a Buchner funnel. The filter cake is rinsed with 3×10 mL of isopropanol at 20–25° C. and transferred to a drying oven and dried in vacuo at 70–75° C. for 43 h. This afforded 4.52 g of anhydrous ziprasidone hydrochloride. The material contained 3.1% and 0.26% of residual NMP and IPA, respectively as determined by NMR.

Workup

  1. customTo a 3-necked flask equipped with mechanical stirrer
  2. temperaturethe suspension was warmed up to 35–40° C. to dissolution
  3. filtrationThe product was collected by filtration on a Buchner funnel
  4. washThe filter cake is rinsed twice with 10 mL of isopropanol at 20–25° C.
  5. customthe damp cake transferred to a flask
  6. customequipped with magnetic stirrer and nitrogen inlet
  7. additionIsopropanol was added (30 mL)
  8. stirringthe suspension stirred at 20–25° C. for about 2 h
  9. filtrationThe product was collected by filtration on a Buchner funnel
  10. washThe filter cake is rinsed with 3×10 mL of isopropanol at 20–25° C.
  11. customtransferred to a drying oven
  12. customdried in vacuo at 70–75° C. for 43 h

Sources & evidence

ORD record
ord-d6f3e0d7fddb4fc9a434ada79b3951cc
Source dataset
uspto-grants-2006_08
Patent number
US07087611B2

Linked notes

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