Ethanol → Ivabradine

HRID 1424383Notes

Reaction equation

HRID 1424383 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][N:14]([CH3:34])[CH2:15][CH2:16][CH2:17][N:18]1[C:24](=[O:25])[CH2:23][C:22]3[CH:26]=[C:27]([O:32][CH3:33])[C:28]([O:30][CH3:31])=[CH:29][C:21]=3[CH:20]=[CH:19]1)[CH2:6]2.C(O)C>[OH-].[OH-].[Pd+2].C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][N:14]([CH3:34])[CH2:15][CH2:16][CH2:17][N:18]1[C:24](=[O:25])[CH2:23][C:22]3[CH:26]=[C:27]([O:32][CH3:33])[C:28]([O:30][CH3:31])=[CH:29][C:21]=3[CH2:20][CH2:19]1)[CH2:6]2

Participants

5

Reactant 2

HCID 702EthanolHCID 161147963-{3-[{[(7S)-3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino]propyl}-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

Product 1

HCID 132999Ivabradine

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 176Acetic AcidSolvent

Procedure

In a 250-ml autoclave, 4 g of the product obtained in Example 1 and 2 g of Pd(OH)2 (20%, 50% moist) are added to a solution of ethanol (90 mL) and acetic acid (10 mL). After remaining in contact for 5 hours at ambient temperature under a hydrogen pressure of 5 bar, the reaction mixture is filtered over Celite®. The residue obtained after concentrating under reduced pressure is taken up in dichloromethane (100 mL) and then washed with saturated aqueous sodium bicarbonate solution. The oil obtained after drying the organic phase over MgSO4 and then concentrating under reduced pressure is purified by chromatography over silica (dichloromethane/ethanol/NH4OH 28%: 95/5/0.5), and 2.6 g of the title product are obtained in the form of an oil.

Workup

  1. filtrationpressure of 5 bar, the reaction mixture is filtered over Celite®
  2. customThe residue obtained
  3. concentrationafter concentrating under reduced pressure
  4. washwashed with saturated aqueous sodium bicarbonate solution
  5. customThe oil obtained
  6. dry with materialafter drying the organic phase over MgSO4
  7. concentrationconcentrating under reduced pressure
  8. customis purified by chromatography over silica (dichloromethane/ethanol/NH4OH 28%: 95/5/0.5), and 2.6 g of the title product
  9. customare obtained in the form of an oil

Sources & evidence

ORD record
ord-13c6aaab7c324288807095c9b2329262
Source dataset
uspto-grants-2015_01
Patent number
US08927708B2

Reaction notes

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