Sulfuric Acid → Clopidogrel bisulfate

HRID 1884867Notes

Reaction equation

HRID 1884867 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)(C)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 33%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Clopidogrel base (2.89 g) was dissolved in isopropanol (44 mL). Eighty percent aqueous sulfuric acid (0.42 mL) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours. The solution was cooled to room temperature and stirred at this temperature for an additional 5 hours. Then half of the solvent was removed by evaporation under reduced pressure and the resulting solution was stirred at room temperature for 45 minutes to obtain a white precipitate. The solid was collected by filtration, washed with IPA (3×10 ml) and dried at 50° C. in a vacuum oven for 15 hours to obtain 1.24 g (33%) of clopidogrel hydrogensulfate crystal Form IV.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 2 hours
  3. customThen half of the solvent was removed by evaporation under reduced pressure
  4. stirringthe resulting solution was stirred at room temperature for 45 minutes
  5. customto obtain a white precipitate
  6. filtrationThe solid was collected by filtration
  7. washwashed with IPA (3×10 ml)
  8. customdried at 50° C. in a vacuum oven for 15 hours

Sources & evidence

ORD record
ord-79162e6372324656b5c7255b2c651226
Source dataset
uspto-grants-2004_07
Patent number
US06767913B2

Reaction notes

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