Sulfuric Acid → Clopidogrel bisulfate

HRID 1792108Notes

Reaction equation

HRID 1792108 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(OCC)(=O)C>[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[C:11]([Cl:12])=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[OH:25][S:22]([OH:26])(=[O:24])=[O:23]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 60606Clopidogrel

Product 1

HCID 115366Clopidogrel bisulfateYield 66%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Clopidogrel base (5.31 g, leq.) was dissolved in ethyl acetate (41.9 mL). Eighty percent aqueous sulfuric acid (1.29 mL, 1.1 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours during which a massive precipitate was formed. Then, the solution was cooled to room temperature and stirred at this temperature for an additional 3 hours. The white solid was collected by filtration, washed with ethyl acetate (2×10 ml) and dried at 50° C. in a vacuum oven for 24 hours to obtain 4.60 g (66%) of clopidogrel hydrogensulfate crystal Form II.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 2 hours during which a massive precipitate
  3. customwas formed
  4. filtrationThe white solid was collected by filtration
  5. washwashed with ethyl acetate (2×10 ml)
  6. customdried at 50° C. in a vacuum oven for 24 hours

Sources & evidence

ORD record
ord-47881f4596bd4cffabd3e61aec361380
Source dataset
uspto-grants-2006_07
Patent number
US07074928B2

Reaction notes

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