Sodium Carbonate → Ticlopidine

HRID 1612937Notes

Reaction equation

HRID 1612937 reaction equation
[S:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[CH:3]=[CH:2]1.[Cl:10][C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[CH2:13]Cl.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[Li+].[Li+]>O.C1COCC1.C(#N)C.ClCCl>[CH:16]1[CH:17]=[CH:18][C:11]([Cl:10])=[C:12]([CH2:13][N:6]2[CH2:5][C:4]3[CH:3]=[CH:2][S:1][C:9]=3[CH2:8][CH2:7]2)[CH:15]=1

Participants

10

Reactant 5

HCID 10340Sodium CarbonateHCID 11125Lithium CarbonateHCID 11430Potassium Carbonate2×HCID 119062-Chlorobenzyl chlorideHCID 30850764,5,6,7-Tetrahydrothieno(3,2-c)pyridine

Product 1

HCID 5472Ticlopidine

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a preferred alkylation procedure, 4,5,6,7-tetrahydrothieno[3,2-c]pyridine in a solvent (e.g., a polar solvent, such as THF, dichloromethane or acetonitrile; preferably 5-15% wet THF) and a compound of Formula 4 (preferably o-chlorobenzyl chloride) are added to a molar excess of a base (e.g., potassium carbonate, sodium carbonate, or lithium carbonate; preferably potassium carbonate) that has been wetted with water (about 5 to 15%, preferably about 10% of the volume charge) and the reaction mixture is refluxed until disappearance of the starting materials is confirmed by tlc (about 8 to 42 hours, preferably about 18-24 hours). The solvent is removed (by vacuum or by displacement with another solvent such as toluene), and the product is washed with water and then concentrated in vacuo. Using the preferred compound of Formula 4, ticlopidine free base (Formula III) is formed (about 90-95% yield) as a light yellow oil. ##STR8##

Workup

  1. additioncharge) and the reaction mixture
  2. temperatureis refluxed until disappearance of the starting materials
  3. customabout 8 to 42 hours, preferably about 18-24 hours
  4. customThe solvent is removed (by vacuum
  5. washby displacement with another solvent such as toluene), and the product is washed with water
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cdb518cdcac74d86a305746265991fc5
Source dataset
uspto-grants-1993_03
Patent number
US05191090

Reaction notes

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