Dimethylformamide → Clopidogrel

HRID 269378Notes

Reaction equation

HRID 269378 reaction equation
Cl.[S:2]1[C:6]2=[CH:7][CH:8]=[CH:9][NH:10][CH:5]2[CH2:4][CH2:3]1.[CH3:11][O:12][C:13](=[O:23])[CH:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:22])Br.CN(C=O)C.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:11][O:12][C:13]([C@@H:14]([N:10]1[CH2:9][C:8]2[CH:7]=[CH:6][S:2][C:3]=2[CH2:4][CH2:5]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:22])=[O:23]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 10730282Methyl alpha-bromo-2-chlorophenylacetateHCID 68420022Tetrahydrothienopyridine hydrochloride

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
82.5 °C

Procedure

50 g (0.284 mole) of Tetrahydrothienopyridine hydrochloride (A) was reacted with 83 g (0.315 mole) of α-bromo-2-chlorophenyl acetic acid methyl ester (B) in 2.5 Lt. DMF in presence of 83 g. (0.6 mole) potassium carbonate. The reaction mixture was heated at 80-85°C under nitrogen atmosphere for 4 Hrs. The reaction mixture was filtered at RT and washed the residue with DMF. The DMF was concentrated under vacuum to obtain a viscous liquid. To this viscous liquid, water was added and the base was extracted from the aqueous layer using methylene dichloride. The methylene dichloride was concentrated under vacuum to get pure Clopidogrel base. Yield =92%

Workup

  1. filtrationThe reaction mixture was filtered at RT
  2. washwashed the residue with DMF
  3. concentrationThe DMF was concentrated under vacuum
  4. customto obtain a viscous liquid
  5. extractionthe base was extracted from the aqueous layer
  6. concentrationThe methylene dichloride was concentrated under vacuum

Sources & evidence

ORD record
ord-f8d663c43c524b5293970af238ab80c6
Source dataset
uspto-grants-2008_11
Patent number
US07446200B2

Reaction notes

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