Ethyl Acetate → (RS)-Clopidogrel

HRID 988862Notes

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]([O-:11])=[O:10].O.[C@:22]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(OCC)(=O)C.C([O-])(O)=O.[Na+]>CC(C)=O.O>[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:11][CH3:22])=[O:10]

Participants

Conditions

Temperature: -2.5 °C

Procedure

2 g (0.0173 mole) Methyl (2-chlorophenyl(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate (where ee was 95%) was dissolved in 10 ml acetone and the reaction mixture was stirred for 10 min, followed by reflux. To the reaction mixture, 1.49 g (1S)-(+)-camphor-10-sulfonic acid hydrate in 0.8 mL water was added followed by 1 mL acetone. Then whole reaction mixture was refluxed for 1 hrs and cooled gradually. This was later stirred overnight at room temperature. The clear solution was cooled further at 0 to −5° C., wherein precipitate was obtained. The salt formed was added to ethyl acetate and water, which was later basified with NaHCO3, the organic layer was washed with water, concentrated under reduced pressure, to give free base 0.386 g with chiral purity=99.85% (+)-isomer (ee=99.7%).

Workup

temperatureby reflux
temperatureThen whole reaction mixture was refluxed for 1 hrs
temperaturecooled gradually
waitThis was later stirred overnight at room temperature
customwherein precipitate was obtained
customThe salt formed
washthe organic layer was washed with water
concentrationconcentrated under reduced pressure
customto give free base 0.386 g with chiral purity=99.85% (+)-isomer (ee=99.7%)

Sources & evidence

ORD record: ord-efad596f09124a00adba541c27b76612
Source dataset: uspto-grants-2003_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06635763B2

Reaction notes

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