Methanol → (RS)-Clopidogrel

HRID 988849Notes

Reaction equation

HRID 988849 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].[CH3:21][OH:22]>>[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:22][CH3:21])=[O:10]

Participants

3

Reactant 2

HCID 887MethanolHCID 113128242-Chlorophenyl-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetamide

Product 1

HCID 2806(RS)-Clopidogrel

Conditions

Temperature
85 °C

Procedure

1 g (0.00326 mol) (±)-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetamide was dissolved in 20 mL methanol and refluxed at 85° C. During the reflux 10 mL polyphosphoric acid was added dropwise over a period of 1 hr and refluxing was continued for 6 hour. The excess of solvent was removed under reduced pressure. To the residue, 50 mL ethyl acetate was added at 0° C. and the reaction mixture was made basic with aq. NaHCO3, up to pH 9. Out of the two phases separated, the organic layer was isolated, dried over anhydrous Na2SO4 and concentrated. The residue obtained was purified by column chromatography using hexane:ethyl acetate (9:1) as eluent. The product obtained was stored under nitrogen atmosphere and kept in refrigerator before converting into salt. The yield of titled product was 310 mg (30%).

Workup

  1. temperaturerefluxing
  2. customThe excess of solvent was removed under reduced pressure
  3. additionTo the residue, 50 mL ethyl acetate was added at 0° C.
  4. customOut of the two phases separated
  5. customthe organic layer was isolated
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customThe residue obtained
  9. customwas purified by column chromatography
  10. customThe product obtained

Sources & evidence

ORD record
ord-1b3677dafa804e159b7958b6867beeae
Source dataset
uspto-grants-2003_10
Patent number
US06635763B2

Reaction notes

Loading…