Acetic Anhydride → Lacosamide

HRID 1844772Notes

Reaction equation

HRID 1844772 reaction equation
[NH2:1][C@H:2]([CH2:13][O:14][CH3:15])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[C:16](OC(=O)C)(=[O:18])[CH3:17]>ClCCl.C(OCC)(=O)C>[CH3:17][C:16]([NH:1][C@@H:2]([C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4])[CH2:13][O:14][CH3:15])=[O:18]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 10104501(R)-2-Amino-N-benzyl-3-methoxypropionamide

Product 1

HCID 219078LacosamideYield 68.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cold solution (−2° C.) of 1.94 g of Intermediate 6, in 40 mL of dichloromethane was added dropwise 2.12 g of acetic anhydride maintaining the temperature below 5° C. The reaction mixture was stirred at room temperature for 3 hours and the organic phase was washed with water (2×20 mL), sodium bicarbonate solution (2×20 mL), brine and dried over sodium sulfate. The solvent was removed under vacuum and a white solid was obtained. The product was dissolved in 20 mL of ethyl acetate at reflux temperature and cooled slowly to 0° C. The solid was collected by filtration and dried yielding 1.6 g of lacosamide as a white solid.

Workup

  1. washthe organic phase was washed with water (2×20 mL), sodium bicarbonate solution (2×20 mL), brine
  2. dry with materialdried over sodium sulfate
  3. customThe solvent was removed under vacuum
  4. customa white solid was obtained
  5. temperatureat reflux temperature
  6. temperaturecooled slowly to 0° C
  7. filtrationThe solid was collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-c67051dab2e04d41a3085fbaa32899af
Source dataset
uspto-grants-2015_02
Patent number
US08946477B2

Reaction notes

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