Hydrochloric Acid → Clopidogrel

HRID 2299276Notes

Reaction equation

HRID 2299276 reaction equation
O[CH:2]1[CH2:7][N:6]([CH: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 13938216(+/-) Methyl alpha-(7-Hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

(±) Methyl α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate (23) (0.21 g, 0.622 mmol) was dissolved in acetic acid (4 mL) and treated sequentially with conc. HCl and SnCl2 dihydrate (0.28 g, 1.243 mmol). The reaction was allowed to stir overnight and the solvent was evaporated under vacuum. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate and the ethyl acetate layer was concentrated to provide clopidogrel free base as an oily product (0.16 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 (4 H, s).

Workup

  1. customthe solvent was evaporated under vacuum
  2. customThe residue was partitioned between ethyl acetate and saturated sodium bicarbonate
  3. concentrationthe ethyl acetate layer was concentrated

Sources & evidence

ORD record
ord-6c1913a2cf984a00952b0ab279d90825
Source dataset
uspto-grants-2002_12
Patent number
US06495691B1

Reaction notes

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