Sulfuric Acid → Clopidogrel bisulfate

HRID 1792102Notes

Reaction equation

HRID 1792102 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]>ClCCl>[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 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Clopidogrel base (3.73 g, leq.) was dissolved in dichloromethane (29.4 mL). Eighty percent aqueous sulfuric acid (0.55 ml, 0.66 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours during which a precipitate was formed. Then, the solution was cooled to room temperature and half of the amount of the solvent was evaporated under reduced pressure. The white solid was collected by filtration, washed with dichloromethane (2×10 ml) and dried at 50° C. in a vacuum oven for 24 hours to obtain 1.42 g (30%) of clopidogrel hydrogensulfate crystal Form I.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 2 hours during which a precipitate
  3. customwas formed
  4. customhalf of the amount of the solvent was evaporated under reduced pressure
  5. filtrationThe white solid was collected by filtration
  6. washwashed with dichloromethane (2×10 ml)
  7. customdried at 50° C. in a vacuum oven for 24 hours

Sources & evidence

ORD record
ord-30d8debe6dd34c569a3ba14a104ccb1b
Source dataset
uspto-grants-2006_07
Patent number
US07074928B2

Reaction notes

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