Sulfuric Acid → Clopidogrel

HRID 988858Notes

Reaction equation

HRID 988858 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].C1(C)C=CC=CC=1.OS(O)(=O)=O.[C:33](=O)([O-])[O-:34].[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:34][CH3:33])=[O:10]

Participants

6

Reactant 4

HCID 1118Sulfuric Acid2×HCID 1140TolueneHCID 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
90 °C

Procedure

5 g of (+)-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetamide was dissolved in 45 ml methanol, followed by 15 mL of toluene. 5 mL (0.28 mol) of conc. H2SO4 was instantly added and another 10 mL of conc. H2SO4 was slowly added later, while maintaining the temperature at 90° C. After that, the reaction mixture was refluxed at 90° C. for 13 hrs. The solvent was distilled off under reduced pressure. To the residue, 50 mL of water was added and 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 2.8 g of crude product purified by column chromatography, using hexane:ethyl acetate (9:1) as eluent.

Workup

  1. temperatureAfter that, the reaction mixture was refluxed at 90° C. for 13 hrs
  2. distillationThe solvent was distilled off under reduced pressure
  3. additionTo the residue, 50 mL of water was added
  4. customthe pH of reaction mixture
  5. extractionThe residue was extracted with 100 mL ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. customevaporated under vacuum
  8. customThe combined eluent was evaporated at reduced pressure

Sources & evidence

ORD record
ord-1318dea66dae40c5b1c8759222e48d13
Source dataset
uspto-grants-2003_10
Patent number
US06635763B2

Reaction notes

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