Sulfuric Acid → Clopidogrel

HRID 988857Notes

Reaction equation

HRID 988857 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([N:12]1[CH2:17][CH2:16][C:15]2[S:18][CH:19]=[CH:20][C:14]=2[CH2:13]1)[C:9](N)=[O:10].OS(O)(=O)=O.[C:26](=O)([O-])[O-:27].[Na+].[Na+]>CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([N:12]1[CH2:17][CH2:16][C:15]2[S:18][CH:19]=[CH:20][C:14]=2[CH2:13]1)[C:9]([O:27][CH3:26])=[O:10]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 113128242-Chlorophenyl-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetamide

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-2.5 °C

Procedure

5 g of (+)-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetamide was dissolved in 35 ml methanol and the solution was chilled to 0 to −5° C. 15 mL (0.28 mole) of conc. H2SO4 (98%) was added slowly in 1 hr maintaining the temperature till −5° C. After the completion of addition the reaction mixture was stirred at room temperature for 30 min. The solution was refluxed at 60° C. for 36 hrs. The reaction mixture was cooled to room temperature and the solvent was distilled off under reduced pressure. The residue was added to 200 mL chilled water was added and cooled to −5° C. The pH of reaction mixture was adjusted between 9 to 10 using aq. sodium carbonate. The residue was extracted with 100 mL ethyl acetate. The organic layer was dried over anhydrous Na2SO4, and evaporated under vacuum. The combined eluent was evaporated at reduced pressure to yield 3.2 g of purified product purified by column chromatography, using hexane: ethyl acetate (9:1) as eluent.

Workup

  1. temperaturemaintaining the temperature till −5° C
  2. additionAfter the completion of addition the reaction mixture
  3. temperatureThe solution was refluxed at 60° C. for 36 hrs
  4. temperatureThe reaction mixture was cooled to room temperature
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionThe residue was added to 200 mL
  7. temperaturechilled water
  8. additionwas added
  9. temperaturecooled to −5° C
  10. customThe pH of reaction mixture
  11. extractionThe residue was extracted with 100 mL ethyl acetate
  12. dry with materialThe organic layer was dried over anhydrous Na2SO4
  13. customevaporated under vacuum
  14. customThe combined eluent was evaporated at reduced pressure

Sources & evidence

ORD record
ord-5ff066fa71264c2aa76c57c1bc7be884
Source dataset
uspto-grants-2003_10
Patent number
US06635763B2

Reaction notes

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