Sulfuric Acid → Clopidogrel bisulfate

HRID 1792109Notes

Reaction equation

HRID 1792109 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(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

4

Reactant 2

HCID 1118Sulfuric AcidHCID 60606Clopidogrel

Product 1

HCID 115366Clopidogrel bisulfateYield 52%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

Clopidogrel base (4.39 g, leq.) was dissolved in tert-butylmethyl ether (MTBE) (34.6 ml). Eighty percent aqueous sulfuric acid (0.64 ml, 0.66 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 3 hours during which a sticky precipitate was formed. Then, the solution was cooled to room temperature and stirred at this temperature for an additional 2 hours. The obtained white 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 2.96 g (52%) of clopidogrel hydrogensulfate crystal Form II.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 3 hours during which a sticky precipitate
  3. customwas formed
  4. filtrationThe obtained white solid was collected by filtration
  5. washwashed with MTBE (2×10 mL)
  6. customdried at 50° C. in a vacuum oven for 24 hours

Sources & evidence

ORD record
ord-0b818c555a26422ca7684099ad68aa00
Source dataset
uspto-grants-2006_07
Patent number
US07074928B2

Reaction notes

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