Formaldehyde → (RS)-Clopidogrel

HRID 1384482Notes

Reaction equation

HRID 1384482 reaction equation
Cl.[S:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH2:7][CH2:8][NH:9][CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])[C:11]([O:13][CH3:14])=[O:12].[CH2:22]=O>ClC(Cl)C.O>[CH3:14][O:13][C:11](=[O:12])[CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])[N:9]1[CH2:8][CH2:7][C:3]2[S:2][CH:6]=[CH:5][C:4]=2[CH2:22]1

Participants

5

Reactant 2

HCID 712FormaldehydeHCID 24820193Methyl 2-(2-chlorophenyl)-2-((2-(thiophen-2-yl)ethyl)amino)acetate hydrochloride

Product 1

HCID 2806(RS)-ClopidogrelYield 90.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

6 g (0.017 mol) of dextrorotatory methyl [2-(2-thienyl)ethylamino](2-chlorophenyl)acetate hydrochloride is suspended in 6.7 ml of 38% aqueous formaline solution and heated to 60° C. under stirring. The starting material dissolves at 60° C., the resulting solution is stirred at the temperature for 30 minutes, till the completion of the reaction. The reaction mixture is then diluted with 100 ml of 1.2 dichloroethane and 150 ml of water, and after shaking well, the phases are separated. The aqueous phase is extracted with 2×30 ml of 1,2-dichloroethane, the united organic phase is extracted with 100 ml of water, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residual 6 g of material is dissolved in 30 ml of diethyl ether, and while cooling the reaction mixture, 0.6 g of dry hdyrogen chloride gas is introduced into the solution, at room temperature. The precipitated crystalline material is filtered off, washed with ether and dried. Weight: 5.5 g. Mp.: 130-132° C., [α]22D=+60°. Yield: 90.1%. Optical purity: 99% (by HPLC investigation).

Workup

  1. dissolutionThe starting material dissolves at 60° C.
  2. stirringthe resulting solution is stirred at the temperature for 30 minutes, till the completion of the reaction
  3. stirringafter shaking well
  4. customthe phases are separated
  5. extractionThe aqueous phase is extracted with 2×30 ml of 1,2-dichloroethane
  6. extractionthe united organic phase is extracted with 100 ml of water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. dissolutionThe residual 6 g of material is dissolved in 30 ml of diethyl ether
  11. temperaturewhile cooling the reaction mixture, 0.6 g of dry hdyrogen chloride gas
  12. additionis introduced into the solution, at room temperature
  13. filtrationThe precipitated crystalline material is filtered off
  14. washwashed with ether
  15. customdried

Sources & evidence

ORD record
ord-8f357088302b4c85aa5f88ea01e87d0c
Source dataset
uspto-grants-2001_07
Patent number
US06258961B1

Reaction notes

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