Acetyl chloride → Agomelatine

HRID 243638Notes

Reaction equation

HRID 243638 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(=O)([O-])[O-].[K+].[K+].[C:23](Cl)(=[O:25])[CH3:24]>O.ClCCl>[CH3:24][C:23]([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:25]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 11430Potassium CarbonateHCID 160500552-(7-Methoxynaphthalen-1-yl)ethan-1-amine hydrochloride

Product 1

HCID 82148AgomelatineYield 78.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

The compound V (6.0 g, 0.03 mol) produced as described above and potassium carbonate (5 g) were added to 20 ml of water and 40 ml of dichloromethane, and stirred for 30 minutes. The aqueous layer was removed. The organic layer was cooled to the temperature of 0° C., and acetyl chloride (7.8 g, 0.1 mol) was added dropwise. A reaction was allowed to proceed at room temperature for 1 hour. 100 ml water was then added, and the reaction solution was extracted with dichloromethane (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 4.8 g of agomelatine. The yield was 78.5%. The melting point was 107-108° C. (in Literature [2], 109° C.).

Workup

  1. customThe aqueous layer was removed
  2. additionwas added dropwise
  3. waitto proceed at room temperature for 1 hour
  4. extractionthe reaction solution was extracted with dichloromethane (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-8c09a56562a740dd8cdb2680dfc6f064
Source dataset
uspto-grants-2014_02
Patent number
US08653281B2

Reaction notes

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