Water → Agomelatine

HRID 243636Notes

Reaction equation

HRID 243636 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[C:11]2[CH2:14][CH2:15][NH2:16])=[CH:6][CH:5]=1.[C:17]([O-])(=[O:19])[CH3:18].[Na+].C(OC(=O)C)(=O)C.O>C(O)C>[CH3:18][C:17]([NH:16][CH2:15][CH2:14][C:11]1[C:12]2[CH:13]=[C:4]([O:3][CH3:2])[CH:5]=[CH:6][C:7]=2[CH:8]=[CH:9][CH:10]=1)=[O:19]

Participants

6

Reactant 4

HCID 962WaterHCID 7918Acetic AnhydrideHCID 517045Sodium AcetateHCID 160500552-(7-Methoxynaphthalen-1-yl)ethan-1-amine hydrochloride

Product 1

HCID 82148AgomelatineYield 86.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The compound V (6.0 g, 0.03 mol) produced as described above and sodium acetate (3.4 g) were dissolved in 70 ml of ethanol, and acetic anhydride (3.4 g, 0.033 mol) was added. The reaction solution was heated and refluxed for one hour. After cooling, about 100 ml of water was added, and the mixture was extracted with ethyl acetate (50 ml*3). The organic phases were combined, dried with anhydrous magnesium sulfate, and filtered to remove the drying agent. The filtrate was concentrated under reduced pressure, to give a solid. The solid was recrystallized in a 2:1 toluene/n-hexane mixture, to produce 5.3 g of agomelatine. The yield was 86.7%. The melting point was 107-109° C. (in Literature [2], 109° C.).

Workup

  1. temperatureThe reaction solution was heated
  2. temperaturerefluxed for one hour
  3. temperatureAfter cooling
  4. extractionthe mixture was extracted with ethyl acetate (50 ml*3)
  5. dry with materialdried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customto remove the drying agent
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customto give a solid
  10. customThe solid was recrystallized in a 2:1 toluene/n-hexane mixture

Sources & evidence

ORD record
ord-dcfea88877a54a3abb46475ed69233c4
Source dataset
uspto-grants-2014_02
Patent number
US08653281B2

Reaction notes

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