Sulfuric Acid → Clopidogrel bisulfate

HRID 1884851Notes

Reaction equation

HRID 1884851 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(Cl)(Cl)Cl>[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 56%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Clopidogrel base (4.24 g, 1 eq.) was dissolved in chloroform (33.4 mL). Eighty percent aqueous sulfuric acid (0.62 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 chloroform (2×10 mL) and dried at 50° C. in a vacuum oven for 24 hours to obtain 3.14 g (56%) of clopidogrel hydrogensulfate crystal form II.

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 chloroform (2×10 mL)
  7. customdried at 50° C. in a vacuum oven for 24 hours

Sources & evidence

ORD record
ord-8a9eddc8dab3464a87c6eb9b2b9a64a6
Source dataset
uspto-grants-2004_07
Patent number
US06767913B2

Reaction notes

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