Dimethyl Sulfate → Lacosamide

HRID 62578Notes

Reaction equation

HRID 62578 reaction equation
[C:1]([NH:4][C@H:5]([CH2:16][OH:17])[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])(=[O:3])[CH3:2].[OH-].[Na+].S(OC)(O[CH3:24])(=O)=O>C(#N)C.CC(C)=O>[CH3:2][C:1]([NH:4][C@@H:5]([C:6]([NH:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:7])[CH2:16][O:17][CH3:24])=[O:3]

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 14798Sodium HydroxideHCID 10889901(R)-N-Benzyl-2-acetamido-3-hydroxypropionamide

Product 1

HCID 219078LacosamideYield 70%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6342AcetonitrileSolvent

Procedure

(R)-2-Acetamido-N-benzyl-3-hydroxypropionamide (25 g, 0.1059 mole) was suspended in 125 ml of acetonitrile at room temperature. To this was added aqueous sodium hydroxide solution (6.3 g in 15 ml, 0.158 mol) drop wise, followed by dimethyl sulfate (26.7 g, 0.211 mole) drop wise. The reaction mixture was stirred for one hour and concentrated under reduced pressure. The resulting residue was dissolved in 200 ml dichloromethane and the solution washed with water (100 ml×3). The organic layer was treated with 1 g charcoal and stirred for one hour. It was filtered and the filtrate was concentrated under reduced pressure. The solid residue obtained was dissolved in acetone and precipitated by adding diisopropyl ether to obtain Lacosamide. (18.5 g, Yield: 70%; chiral HPLC: 99.8% and chemical HPLC: 99.7%)

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in 200 ml dichloromethane
  3. washthe solution washed with water (100 ml×3)
  4. additionThe organic layer was treated with 1 g charcoal
  5. stirringstirred for one hour
  6. filtrationIt was filtered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe solid residue obtained
  9. customprecipitated
  10. additionby adding diisopropyl ether

Sources & evidence

ORD record
ord-cc49175ea950435d9a4393039a428ed3
Source dataset
uspto-grants-2016_09
Patent number
US09447024B1

Reaction notes

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