Sulfuric Acid → Clopidogrel bisulfate
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
Product 1
Reagents, catalysts & solvents 1
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 reflux 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
- temperatureThe reaction mixture was heated
- temperatureto reflux temperature for 2 hours
- customThen the solvent was evaporated to dryness under reduced pressure
- customto obtain oil
- stirringthe resulting mixture was stirred at room temperature for 16 hours
- filtrationThe precipitate was collected by filtration
- washwashed with DEE (2×10 mL)
- customdried at 50° C. in a vacuum oven for 19 hours
Sources & evidence
- ORD record
- ord-647c972a68e548229886d01785b179a1
- Source dataset
- uspto-grants-2004_07
- Patent number
- US06767913B2
Reaction notes
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