Sodium Iodide → Clopidogrel

HRID 1828903Notes

Reaction equation

HRID 1828903 reaction equation
[I-].[Na+].Cl[Si](C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:19][O:20][C:21](=[O:40])[C@H:22]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:39])[N:23]1[CH2:28][CH:27](O)[C:26]2[S:30][CH:31]=[CH:32][C:25]=2[CH2:24]1.C(=O)(O)[O-].[Na+]>C(#N)C>[CH3:19][O:20][C:21]([C@@H:22]([N:23]1[CH2:24][C:25]2[CH:32]=[CH:31][S:30][C:26]=2[CH2:27][CH2:28]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:39])=[O:40]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 21029881HCID 21029881, compound

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of sodium iodide in acetonitrile is added chlorotrimethylsilane. The mixture is stirred at room temperature under nitrogen for 1 hour. (αS,7RS)-methyl-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate para toluenesulfonic acid salt (55.0 g, 108 mmol) is added to the mixture at 0–5° C. After the addition is complete the mixture is warmed to room temperature and stirred for 17 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 oily product (30.6 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. temperatureis warmed to room temperature
  3. stirringstirred for 17 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-113b9ef748ba4fa1bb533006da1aba17
Source dataset
uspto-grants-2006_06
Patent number
US07060831B2

Reaction notes

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