拉科酰胺的合成

Synthesis of Lacosamide

以D-丝氨酸为原料,经酯化、用(Boc)2O保护氨基得(R)-3-羟基-2-[(叔丁基氧羰基)氨基]丙酸甲酯,与苄胺反应得(R)-3-羟基-2-[(叔丁基氧羰基)氨基]丙酰苄胺,低温下经硫酸二甲酯醚化、浓盐酸脱保护得(R)-3-甲氧基-2-氨基丙酰苄胺,最后经乙酐乙酰化得拉科酰胺,总收率为39.3%。

D-serine underwent the esterification and protection with （Boc） 2O to obtain methyl （R）-3-hydroxy-2-（tert-butoxy） carbonyl aminopropanoate,from which （R）-3-hydroxy-2-[（tert-butoxycarbonyl） amino] propionyl benzylamine was prepared.In the condition of cool temperature,（R）-2-amino-N-benzyl-3-methoxypropanamide was generated with the etherification of dimethyl sulfate and deprotection by concentrated hydrochloric acid.Finally,lacosamide was prepared through acetylation with acetic anhydride,with the total yield of 39.3 ％.