Sulfuric Acid → Clopidogrel bisulfate

HRID 1792114Notes

Reaction equation

HRID 1792114 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)CCC.C(OC)(C)(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

5

Reactant 2

HCID 1118Sulfuric AcidHCID 60606Clopidogrel

Product 1

HCID 115366Clopidogrel bisulfateYield 60%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Clopidogrel base (4.28 g) was dissolved in 1-butanol (16.9 ml). Eighty percent aqueous sulfuric acid (0.63 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 the solvent was evaporated to dryness under reduced pressure leaving yellow oil. The oil was stirred in methyl t-butyl ether (MTBE) (125 ml) for 96 hours at room temperature to obtain a precipitate. The solid was collected by filtration, washed with MTBE (2×10 ml) and dried at 50° C. in a vacuum oven for 24 hours to obtain 3.33 g (60%) of clopidogrel hydrogensulfate crystal Form III.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 2 hours
  3. customthe solvent was evaporated to dryness under reduced pressure
  4. customleaving yellow oil
  5. customto obtain a precipitate
  6. filtrationThe solid was collected by filtration
  7. washwashed with MTBE (2×10 ml)
  8. customdried at 50° C. in a vacuum oven for 24 hours

Sources & evidence

ORD record
ord-ac280c140bb948b98b2c2e9fe6e65d9d
Source dataset
uspto-grants-2006_07
Patent number
US07074928B2

Reaction notes

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