Acetic Anhydride → Lacosamide

HRID 2407631Notes

Reaction equation

HRID 2407631 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]>>[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

3

Reactant 2

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

Product 1

HCID 219078Lacosamide

Procedure

The (R)-2-amino-N-benzyl-3-methoxypropionamide solution prepared above was cooled to <5° C. and acetic anhydride (10 ml, 0.106 mol) added at <15° C. The reaction mixture is warmed to room temperature over 30 minutes and aged for a further 30 minutes. The mixture is then washed with water (44 ml), 8% sodium bicarbonate (44 ml) and water (44 ml). The methylene chloride was exchanged for ethyl acetate by distillation and the solution distilled to a volume of 115 ml. The product was crystallised by cooling the solution to 0-5° C. and the pure Lacosamide isolated by filtration (18.7 g, 69.8%) HPLC purity 99.98%, Chiral purity 99.8% ee.

Workup

  1. temperatureabove was cooled to <5° C.
  2. washThe mixture is then washed with water (44 ml), 8% sodium bicarbonate (44 ml) and water (44 ml)
  3. distillationThe methylene chloride was exchanged for ethyl acetate by distillation
  4. distillationthe solution distilled to a volume of 115 ml
  5. customThe product was crystallised
  6. temperatureby cooling the solution to 0-5° C.

Sources & evidence

ORD record
ord-bcd706ee98ee478aa60cc25ea5ac4654
Source dataset
uspto-grants-2014_08
Patent number
US08809585B2

Reaction notes

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