Sulfuric Acid → Clopidogrel bisulfate

HRID 1884846Notes

Reaction equation

HRID 1884846 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]>CC(CC)=O>[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 54%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

Clopidogrel base (5.01 g, 1 eq.) was dissolved in methylethyl ketone (MEK) (39.5 mL). Eighty percent aqueous sulfuric acid (0.74 mL, 0.66 eq.) 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 half of the amount of the solvent was evaporated under reduced pressure during which a precipitate was formed. The white solid was collected by filtration, washed with MEK (2×10 ml) and dried at 50° C. in a vacuum oven for 24 hours to obtain 3.55 g (54%) of clopidogrel hydrogensulfate crystal form II.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 2 hours
  3. customhalf of the amount of the solvent was evaporated under reduced pressure during which a precipitate
  4. customwas formed
  5. filtrationThe white solid was collected by filtration
  6. washwashed with MEK (2×10 ml)
  7. customdried at 50° C. in a vacuum oven for 24 hours

Sources & evidence

ORD record
ord-05b68fbab8864c5fb966e2c70a3c3735
Source dataset
uspto-grants-2004_07
Patent number
US06767913B2

Reaction notes

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