Hydrochloric Acid → Ivabradine Hydrochloride
Reaction equation
[CH3:1][N:2]([CH2:22][C@@H:23]1[C:26]2[CH:27]=[C:28]([O:33][CH3:34])[C:29]([O:31][CH3:32])=[CH:30][C:25]=2[CH2:24]1)[CH2:3][CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][C:14]2[C:9](=[CH:10][C:11]([O:20][CH3:21])=[C:12]([O:18][CH3:19])[CH:13]=2)[CH2:8][CH2:7]1.[ClH:35]>CC(C)=O.C(OCC)(=O)C>[CH3:1][N:2]([CH2:22][C@@H:23]1[C:26]2[CH:27]=[C:28]([O:33][CH3:34])[C:29]([O:31][CH3:32])=[CH:30][C:25]=2[CH2:24]1)[CH2:3][CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][C:14]2[C:9](=[CH:10][C:11]([O:20][CH3:21])=[C:12]([O:18][CH3:19])[CH:13]=2)[CH2:8][CH2:7]1.[ClH:35]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
Acid addition salt of ivabradine is hydrolyzed with a suitable base in demineralized water to get ivabradine. The base can be selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate and preferably sodium hydroxide is used. After complete hydrolysis, the desired compound is extracted in organic solvent. The organic solvent can be selected from halogenated hydrocarbon and aliphatic esters and preferably ethyl acetate is used. Ethyl acetate is distilled out to isolate the ivabradine as oil. Crude ivabradine is further dissolved in a suitable organic solvent such as acetone, ethyl acetate preferably in acetone. The pH of the resulting clear solution is adjusted to 1.0 to 2.0 with alcoholic hydrogen chloride and stirred for 30 to 60 minutes to get highly pure amorphous ivabradine hydrochloride. It is advantageous to dry the organic layer using drying agent such as sodium sulfate or the like before adding alcoholic hydrogen chloride.
Sources & evidence
- ORD record
- ord-fb3b6ad8aa2b4ea29e31b4f14deee7e6
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08212026B2
Reaction notes
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