Sulfuric Acid → Clopidogrel bisulfate

HRID 1884866Notes

Reaction equation

HRID 1884866 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 13%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Clopidogrel base (2.95 g) was dissolved in isopropanol (45 ml). Forty percent aqueous sulfuric acid (1.15 mL) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours. Then, the solution was cooled to room temperature and stirred at this temperature for an additional 3.5 hours to obtain a white precipitate. The solid was collected by filtration, washed with IPA (2×10 mL) and dried at 50° C. in a vacuum oven for 14.5 hours to obtain 0.49 g (13%) of clopidogrel hydrogensulfate crystal Form IV.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 2 hours
  3. customto obtain a white precipitate
  4. filtrationThe solid was collected by filtration
  5. washwashed with IPA (2×10 mL)
  6. customdried at 50° C. in a vacuum oven for 14.5 hours

Sources & evidence

ORD record
ord-53e702c01dab40f6bcd1d685acb996d8
Source dataset
uspto-grants-2004_07
Patent number
US06767913B2

Reaction notes

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