Ethanol → Agomelatine

HRID 2193968Notes

Reaction equation

HRID 2193968 reaction equation
[CH2:1]([OH:3])[CH3:2].O.[H][H].[CH3:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[C:16]2[CH2:19][C:20]#[N:21])=[CH:11][CH:10]=1>[Ni].C(OC(=O)C)(=O)C>[CH3:7][O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[C:16]2[CH2:19][CH2:20][NH:21][C:1](=[O:3])[CH3:2])=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 962WaterHCID 112640682-(7-Methoxynaphthalen-1-yl)acetonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 82148AgomelatineYield 89%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 7918Acetic AnhydrideSolvent

Procedure

There are introduced into an 8 litre reactor 136 g of Raney nickel, 2.06 litres of ethanol and 0.23 litre of water. Whilst stirring at 70° C. and under 30 bars of hydrogen, the compound obtained in Step B (0.8 kg), dissolved in acetic anhydride (2.4 litres), is added slowly. At the end of the addition, the reaction mixture is stirred for 1 hour under hydrogen at 30 bars; the reactor is then subjected to decompression and the liquors are filtered. After concentrating the mixture, the residue is crystallised from an ethanol/water 35/65 mixture to yield the title product in a yield of 89% and with a chemical purity of more than 99%.

Workup

  1. additionis added slowly
  2. additionAt the end of the addition
  3. filtrationthe liquors are filtered
  4. concentrationAfter concentrating the mixture
  5. customthe residue is crystallised from an ethanol/water 35/65 mixture

Sources & evidence

ORD record
ord-11be06cceb5f4b8987904bc0ef89ee86
Source dataset
uspto-grants-2012_12
Patent number
US08329947B2

Reaction notes

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