Methanol → (RS)-Clopidogrel

HRID 988850Notes

Reaction equation

HRID 988850 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].C1(C)C=CC=CC=1.[CH3:28][OH:29]>[Ti](Cl)(Cl)(Cl)Cl>[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:29][CH3:28])=[O:10]

Participants

5

Reactant 3

HCID 887MethanolHCID 1140TolueneHCID 113128242-Chlorophenyl-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetamide

Product 1

HCID 2806(RS)-Clopidogrel

Reagents, catalysts & solvents 1

HCID 24193Titanium TetrachlorideCatalyst

Procedure

1 g (0.00326 mol) (±)-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetamide was added to 2 mL toluene at 0° C. along with stirring, followed by dropwise addition of 1 mL titanium tetrachloride, and the reaction was stirred at 0° C. for 1 hour. Later 18 mL of methanol was added, and then the reaction was stirred for 36 hour at 29° C. and later reflux for 3 hrs. The solvent was distilled under reduced pressure and the residue was added to aq. sodium carbonate at 0° C. the product was extracted with 20 mL ethyl acetate, and the organic layer was isolated, dried over anhy. Na2SO4, concentrated and purified by column chromatography using hexane:ethyl acetate as eluent. The product obtained was stored under nitrogen atmosphere and kept in refrigerator before converting into salt. The yield of titled product was 0.157 g (12-15%).

Workup

  1. stirringthe reaction was stirred at 0° C. for 1 hour
  2. stirringthe reaction was stirred for 36 hour at 29° C.
  3. temperaturelater reflux for 3 hrs
  4. distillationThe solvent was distilled under reduced pressure
  5. additionthe residue was added to aq. sodium carbonate at 0° C. the product
  6. extractionwas extracted with 20 mL ethyl acetate
  7. customthe organic layer was isolated
  8. customdried over anhy
  9. concentrationNa2SO4, concentrated
  10. custompurified by column chromatography
  11. customThe product obtained

Sources & evidence

ORD record
ord-5344d462ab054d0e84cc2c5d4e1e676a
Source dataset
uspto-grants-2003_10
Patent number
US06635763B2

Reaction notes

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