Sulfuric Acid → Clopidogrel bisulfate

HRID 1884859Notes

Reaction equation

HRID 1884859 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(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 56%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Clopidogrel base (3.85 g) was dissolved in absolute ethanol (30.4 mL). Eighty percent aqueous sulfuric acid (0.56 mL) was added to the solution. 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 a white foam. The foam was stirred in methyl t-butyl ether (MTBE) (70 ml) for 3 hours at room temperature. Approximately half of the MTBE was evaporated under reduced pressure and a solid was recovered by filtration. The solid was dried at 50° C. in a vacuum oven to obtain 2.82 g (56%) of a mixture of clopidogrel hydrogensulfate crystal form I and amorphous clopidogrel hydrogensulfate.

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 a white foam
  5. customApproximately half of the MTBE was evaporated under reduced pressure
  6. filtrationa solid was recovered by filtration
  7. customThe solid was dried at 50° C. in a vacuum oven

Sources & evidence

ORD record
ord-046439837e5a4d0f9020586e8f4a0595
Source dataset
uspto-grants-2004_07
Patent number
US06767913B2

Reaction notes

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