Sodium Iodide → Clopidogrel

HRID 1828905Notes

Reaction equation

HRID 1828905 reaction equation
[I-].[Na+].Cl[Si](CC)(CC)CC.S(=O)(=O)(O)O.[CH3:16][O:17][C:18](=[O:37])[C@H:19]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:36])[N:20]1[CH2:25][CH:24](O)[C:23]2[S:27][CH:28]=[CH:29][C:22]=2[CH2:21]1.C(=O)(O)[O-].[Na+]>C(#N)C.CC(C)=O>[CH3:16][O:17][C:18]([C@@H:19]([N:20]1[CH2:21][C:22]2[CH:29]=[CH:28][S:27][C:23]=2[CH2:24][CH2:25]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:36])=[O:37]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 13819ChlorotriethylsilaneHCID 516892Sodium BicarbonateHCID 21029879HCID 21029879, compound

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6342AcetonitrileSolvent

Procedure

To a mixture of sodium iodide in acetonitrile, and acetone is added chlorotriethylsilane. 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 bisulfate salt 25.0 g, 66.8 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 12 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 (20.6 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 12 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-5d93e4c9edee4581b5fed68c732ece01
Source dataset
uspto-grants-2006_06
Patent number
US07060831B2

Reaction notes

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