Hydrochloric Acid → Clopidogrel

HRID 2299277Notes

Reaction equation

HRID 2299277 reaction equation
O[CH:2]1[CH2:7][N:6]([C@@H:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])[C:9]([O:11][CH3:12])=[O:10])[CH2:5][C:4]2[CH:20]=[CH:21][S:22][C:3]1=2.Cl>C(O)(=O)C>[CH3:12][O:11][C:9]([C@@H:8]([N:6]1[CH2:5][C:4]2[CH:20]=[CH:21][S:22][C:3]=2[CH2:2][CH2:7]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])=[O:10]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 11325212HCID 11325212, compound

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Methyl(S)-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate (1 g, 2.95 mmol) was dissolved in acetic acid (18.8 mL) and treated sequentially with conc. HCl and SnCl2 dihydrate (1.4 g, 6.2 mmol). The reaction was allowed to stir under nitrogen and the solvent was evaporated under vacuum after its completion. The residue was basified with aqueous sodium bicarbonate and extracted repeatedly with ethyl acetate. The combined organic layer was dried, filtered and concentrated to provide clopidogrel free base as an oily product (0.75 g). 1H-NMR (CDCl3, ppm) 7.7 (1H, dd), 7.35 (1H, m), 7.2-7-35 (2H, m), 7.2 (1H, d), 6.68 (1H, dd), 4.95 (1H, s), 4.68 (1H, bs), 3.5-4.0 (2H, m), 3.75 (3H, s), 2.9 (4H, s); chiral HPLC 98:2 enantiomeric ratio.

Workup

  1. customthe solvent was evaporated under vacuum after its completion
  2. extractionextracted repeatedly with ethyl acetate
  3. customThe combined organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7cd68d4fdd3b4f1886ad4785ee6d7d78
Source dataset
uspto-grants-2002_12
Patent number
US06495691B1

Reaction notes

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