Water → Clopidogrel

HRID 1828907Notes

Reaction equation

HRID 1828907 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C@H:4]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])[N:5]1[CH2:10][CH:9](O)[C:8]2[S:12][CH:13]=[CH:14][C:7]=2[CH2:6]1.I[Si](C)(C)C.O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(#N)C>[CH3:1][O:2][C:3]([C@@H:4]([N:5]1[CH2:6][C:7]2[CH:14]=[CH:13][S:12][C:8]=2[CH2:9][CH2:10]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])=[O:22]

Participants

7

Reactant 4

HCID 962WaterHCID 85247Trimethylsilyl iodideHCID 516892Sodium BicarbonateHCID 11325212HCID 11325212, compound

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent2×

Procedure

A solution of (αS,7RS)-methyl-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate (9) (59.79 g, 177.0 mmol) in toluene and acetonitrile is added to a solution of iodotrimethylsilane in acetonitrile at 0–5° C. After the addition is complete the mixture is warmed to room temperature and stirred for 2 hours. Water is then added to the mixture at 0–5° C. The mixture is then warmed again to room temperature and stirred for an additional 4 hours. The reaction mixture is then basified with aqueous sodium bicarbonate solution. The organic layer is then washed with aqueous sodium thiosulfate solution, followed by water, then brine. The organic layer is then dried, filtered and concentrated to provide clopidogrel free base as an oil product (55.8 g). The product obtained was found to be identical to the product obtained in Example 1 by 1H-NMR.

Workup

  1. additionAfter the addition
  2. temperatureThe mixture is then warmed again to room temperature
  3. stirringstirred for an additional 4 hours
  4. washThe organic layer is then washed with aqueous sodium thiosulfate solution
  5. customThe organic layer is then dried
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-465c392a3389448e9274593b70d5bbb2
Source dataset
uspto-grants-2006_06
Patent number
US07060831B2

Reaction notes

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