880468-89-3

1253790-58-7

77-78-1

880468-89-3

The general procedure for the synthesis of (R)-2-tert-butoxycarbonylamino-N-benzyl-3-methoxypropanamide from tert-butyl (R)-(1-(phenylmethylamino)-3-hydroxy-1-oxopropan-2-yl)carbamate and dimethyl sulfate was as follows: toluene (4.8 L) was added to a reactor at room temperature, followed by the addition of the Lacosamide Phase II product (1 kg) , and the mixture was cooled to 0°C. Sodium hydroxide solution (0.54 kg), tetrabutylammonium bromide (0.186 kg) and dimethyl sulfate (0.86 kg) were added sequentially, and then the reaction mixture was heated to 30°C with continuous stirring for 90 minutes. After completion of the reaction, the organic phase was separated by extraction with toluene and washed by adding 5% sodium bicarbonate solution. Cyclohexane was added to the organic phase and stirred for 10 minutes, followed by concentration under reduced pressure at 50°C for 2 hours. Finally, the product was dried to give lacosamide III in about 96.28% yield.