Hydrochloric Acid → Ziprasidone Hydrochloride

HRID 1925226Notes

Reaction equation

HRID 1925226 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]2[S:9][N:8]=[C:7]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]4[CH:19]=[C:20]5[CH2:28][C:26](=[O:27])[NH:25][C:21]5=[CH:22][C:23]=4[Cl:24])[CH2:12][CH2:11]3)[C:5]=2[CH:6]=1.[ClH:29]>ClCCl>[CH:1]1[CH:2]=[CH:3][C:4]2[S:9][N:8]=[C:7]([N:10]3[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][C:18]4[CH:19]=[C:20]5[CH2:28][C:26](=[O:27])[NH:25][C:21]5=[CH:22][C:23]=4[Cl:24])[CH2:14][CH2:15]3)[C:5]=2[CH:6]=1.[ClH:29]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 60854Ziprasidone

Product 1

HCID 219099Ziprasidone Hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
32.5 °C

Procedure

To substantially pure ziprasidone base (100 g), was added dichloromethane (2.0 Lit) and stirred for 15-20 minutes at 30-35° C. To this, was added ethereal solution of hydrogen chloride (95.7 ml) over a period of 5-10 min at 30-35° C. under stirring. The suspension was further stirred for 17-20 hours at 32-35° C. and separated solids were filtered under vacuum and nitrogen atmosphere at 32-35° C. The wet solid was washed with diethyl ether (100 ml) and was suspended in water (500 ml) at 20-25° C. It was stirred for 30 minutes at 20-25° C. The mass was filtered and re-suspended in water (500 ml) and after stirring for approximately 1 hour, the cake was filtered and washed with a pre-cooled mixture of water and isopropanol (2×250 ml, 1:0.25). The washings were found to be free of acidity (pH of about 7). The product obtained was dried under vacuum at 55-60° C. for 12-15 hours till the moisture content was less than 0.5% w/w.

Workup

  1. stirringunder stirring
  2. stirringThe suspension was further stirred for 17-20 hours at 32-35° C.
  3. customseparated solids
  4. filtrationwere filtered under vacuum and nitrogen atmosphere at 32-35° C
  5. washThe wet solid was washed with diethyl ether (100 ml)
  6. customwas suspended in water (500 ml) at 20-25° C
  7. stirringIt was stirred for 30 minutes at 20-25° C
  8. filtrationThe mass was filtered
  9. stirringafter stirring for approximately 1 hour
  10. filtrationthe cake was filtered
  11. washwashed with a pre-cooled mixture of water and isopropanol (2×250 ml, 1:0.25)
  12. customThe product obtained
  13. customwas dried under vacuum at 55-60° C. for 12-15 hours till the moisture content

Sources & evidence

ORD record
ord-25dea3fbdb1241469172c57cd51c906b
Source dataset
uspto-grants-2012_05
Patent number
US08178674B2

Reaction notes

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