Water → Clopidogrel bisulfate

HRID 1401055Notes

Reaction equation

HRID 1401055 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]([N:13]1[CH2:21][C:17]2[CH:18]=[CH:19][S:20][C:16]=2[CH2:15][CH2:14]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=1[Cl:12])=[O:4].O.[S:23](=[O:27])(=[O:26])([OH:25])[OH:24]>C(O)CCCCC>[CH3:1][O:2][C:3]([C@@H:5]([N:13]1[CH2:21][C:17]2[CH:18]=[CH:19][S:20][C:16]=2[CH2:15][CH2:14]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=1[Cl:12])=[O:4].[OH:26][S:23]([OH:27])(=[O:25])=[O:24]

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 60606Clopidogrel

Product 1

HCID 115366Clopidogrel bisulfate

Reagents, catalysts & solvents 1

HCID 81031-HexanolSolvent

Conditions

Temperature
27.5 °C

Procedure

Clopidogrel base (250 gms) was dissolved in n-hexanol (1.25 L) with stirring at 25 to 30° C. and water (5 ml) was added followed by addition of concentrated sulfuric acid at 10 to 15° C. The mixture was stirred at room temperature, for 6 hrs and subsequently it was stirred at 22 to 25° C., for 5 hours at high agitation. The reaction mixture was further stirred for 4 hours at room temperature at low agitation. The mixture was then filtered, washed with methyl tert-butyl ether (750 ml) and dried at 30 to 35° C. in a drier, to get 280 g of Clopidogrel bisulfate salt as crystals. Subsequent analysis confirmed that the crystals were Clopidogrel hydrogen sulfate Form-I.

Workup

  1. stirringThe mixture was stirred at room temperature, for 6 hrs
  2. stirringsubsequently it was stirred at 22 to 25° C., for 5 hours at high agitation
  3. stirringThe reaction mixture was further stirred for 4 hours at room temperature at low agitation
  4. filtrationThe mixture was then filtered
  5. washwashed with methyl tert-butyl ether (750 ml)
  6. customdried at 30 to 35° C. in a drier

Sources & evidence

ORD record
ord-62f1187aaa6949799e3686a884e4970a
Source dataset
uspto-grants-2014_12
Patent number
US08907090B2

Reaction notes

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