Sulfuric Acid → Clopidogrel bisulfate

HRID 1884853Notes

Reaction equation

HRID 1884853 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 49%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Clopidogrel base (4.03 g, 1 eq.) was dissolved in ethyl acetate (31.8 mL). Eighty percent aqueous sulfuric acid (0.59 mL, 0.66 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 3 hours during which a sticky precipitate was formed. Then, the solution was cooled to room temperature and stirred at this temperature for an additional 16 hours during which a massive precipitate was formed. 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 2.59 g (49%) of clopidogrel hydrogensulfate crystal form II.

Workup

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

Sources & evidence

ORD record
ord-9cf2ff2b55ba423491f11a3c73fd9f48
Source dataset
uspto-grants-2004_07
Patent number
US06767913B2

Reaction notes

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