Sulfuric Acid → Clopidogrel bisulfate

HRID 1792124Notes

Reaction equation

HRID 1792124 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)C>CC(O)CC>[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

5

Reactant 3

HCID 1118Sulfuric AcidHCID 3283Diethyl EtherHCID 60606Clopidogrel

Product 1

HCID 115366Clopidogrel bisulfateYield 55%

Reagents, catalysts & solvents 1

HCID 6568(+-)-2-ButanolSolvent

Procedure

Clopidogrel base (2.94 g) was dissolved in 2-butanol (23 mL). Ninety eight percent aqueous sulfuric acid (0.43 mL) was added to the solution at 20° C. The reaction mixture was heated to reflex temperature for 2 hours. The solution was cooled to room temperature and stirred at this temperature for additional 1.5 hours. Then the solvent was evaporated to dryness under reduced pressure to obtain oil. Then diethyl ether (DEE) (40 ml) was added to the oily residue and the resulting mixture was stirred at room temperature for 16 hours. The precipitate was collected by filtration, washed with DEE (2×10 mL) and dried at 50° C. in a vacuum oven for 19 hours to obtain 2.11 g (55%) of clopidogrel hydrogensulfate crystal Form V.

Workup

  1. temperatureThe reaction mixture was heated
  2. customfor 2 hours
  3. customThen the solvent was evaporated to dryness under reduced pressure
  4. customto obtain oil
  5. stirringthe resulting mixture was stirred at room temperature for 16 hours
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with DEE (2×10 mL)
  8. customdried at 50° C. in a vacuum oven for 19 hours

Sources & evidence

ORD record
ord-e10d3fa053c0492dba9696b145cfbfd8
Source dataset
uspto-grants-2006_07
Patent number
US07074928B2

Reaction notes

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