Sulfuric Acid → Clopidogrel bisulfate

HRID 1401047Notes

Reaction equation

HRID 1401047 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].[S:22](=[O:26])(=[O:25])([OH:24])[OH:23]>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:25][S:22]([OH:26])(=[O:24])=[O:23]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 60606Clopidogrel

Product 1

HCID 115366Clopidogrel bisulfate

Reagents, catalysts & solvents 1

HCID 81031-HexanolSolvent

Conditions

Temperature
27.5 °C

Procedure

Clopidogrel base (925 gms) was dissolved in n-hexanol (4.6 L) with stirring at 25 to 30° C. Dilute sulfuric acid was added to the reaction mixture at 10 to 15° C. The mixture was seeded with form-I crystal at 20 to 25° C. The reaction mixture was stirred for approximately 8 to 10 hours & subsequently further stirred for 8-10 hrs at 22 to 25° C. with low agitation. The solid was then filtered and washed with methyl tert butyl ether (1875 ml) and subsequently dried at 30 to 35° C. on a drier, to get 1095 g of clopidogrel bisulfate salt as crystals. Subsequent analysis confirmed that the crystals were clopidogrel hydrogen sulfate Form-I.

Workup

  1. customwas seeded with form-I crystal at 20 to 25° C
  2. stirringThe reaction mixture was stirred for approximately 8 to 10 hours
  3. stirringsubsequently further stirred for 8-10 hrs at 22 to 25° C. with low agitation
  4. filtrationThe solid was then filtered
  5. washwashed with methyl tert butyl ether (1875 ml)
  6. customsubsequently dried at 30 to 35° C. on a drier

Sources & evidence

ORD record
ord-503fdb2a4a124737bfe7c59839d01876
Source dataset
uspto-grants-2014_12
Patent number
US08907090B2

Reaction notes

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