Methanol → (RS)-Clopidogrel
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].CS(O)(=O)=O.[CH3:26][OH:27]>>[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]([O:27][CH3:26])=[O:10]Participants
Conditions
- Temperature
- 85 °C
Procedure
2 g (0.00652 mol) (±)-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetamide and 2 mL (0.0308 mol) methane sulfonic acid and 20 mL methanol were mixed and the solution was refluxed at 85° C. for 12 hrs. The excess of solvent was removed under reduced pressure. The pH was adjusted to about 9 with aq. solution of sodium bicarbonate at 0° C., and the product was extracted with 70 mL ethyl acetate. The combined organic extracts were dried over anhy. Na2SO4 and concentrated. The residue obtained was purified by column chromatography using hexane:ethyl acetate as eluent. The product thus obtained was concentrated, was stored under nitrogen atmosphere, and kept in refrigerator before converting into salt. The yield of titled product was 0.419 g (20%).
Workup
- customThe excess of solvent was removed under reduced pressure
- customwas adjusted to about 9 with aq. solution of sodium bicarbonate at 0° C.
- extractionthe product was extracted with 70 mL ethyl acetate
- customThe combined organic extracts were dried over anhy
- concentrationNa2SO4 and concentrated
- customThe residue obtained
- customwas purified by column chromatography
- customThe product thus obtained
- concentrationwas concentrated
Sources & evidence
- ORD record
- ord-e7efa962a8c34306a597d86df499f611
- Source dataset
- uspto-grants-2003_10
- Patent number
- US06635763B2
Reaction notes
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