Sodium Iodide → Clopidogrel

HRID 1828906Notes

Reaction equation

HRID 1828906 reaction equation
[I-].[Na+].Cl[Si](CC)(CC)CC.[CH3:11][O:12][C:13](=[O:32])[C@H:14]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Cl:31])[N:15]1[CH2:20][CH:19](O)[C:18]2[S:22][CH:23]=[CH:24][C:17]=2[CH2:16]1.C(=O)(O)[O-].[Na+]>ClCCl.O>[CH3:11][O:12][C:13]([C@@H:14]([N:15]1[CH2:16][C:17]2[CH:24]=[CH:23][S:22][C:18]=2[CH2:19][CH2:20]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Cl:31])=[O:32]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 13819ChlorotriethylsilaneHCID 516892Sodium BicarbonateHCID 11325212HCID 11325212, compound

Product 1

HCID 60606Clopidogrel

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of sodium iodide in dichloromethane is added chlorotriethylsilane. The mixture is stirred at room temperature under nitrogen for 90 min. A solution of (αS,7RS)-methyl-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate (9) (8.2 g, 24.3 mmol) in dichloromethane is added to the mixture at 0–5° C. After the addition is complete the mixture is warmed to room temperature and stirred for 3 hours. Water is then added to the mixture at 0–5° C. 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 (6.69 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 3 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-9983b3a2000446c5b82ade4a42362588
Source dataset
uspto-grants-2006_06
Patent number
US07060831B2

Reaction notes

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