Dimethyl Sulfate → Lacosamide

Participants

Reaction Steps

(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%)

Provenance & Evidence