布瓦西坦中间体(R)-4-丙基-二氢呋喃-2-酮的合成工艺  

Synthesis of (R)-4-Propyldihydrofuran-2(3H)-one, an Intermediate of Brivaracetam

作　　者：李耀锋 李立斌 靳晓坤 温海珊 LI Yao-feng;LI Li-bin;JIN Xiao-kun;WEN Hai-shan(Shijiazhuang Chirals Chemical Co.Ltd.,Shijiazhuang 050000,China)

机构地区：[1]石家庄手性化学有限公司,河北石家庄050000

出　　处：《安徽化工》2021年第6期100-102,共3页Anhui Chemical Industry

摘　　要：报道了布瓦西坦的关键中间体(R)-4-丙基-二氢呋喃-2-酮(1)的新合成工艺。以戊醛和乙醛酸为起始原料,在吗啉的催化下反应得到中间体5-羟基-4-正丙基-2-呋喃酮,然后用硼氢化钠脱去5位上的羟基得到中间体4-正丙基-2-呋喃酮,最后在手性膦配体SBINAP的催化作用下,进行不对称还原得到目标化合物(R)-4-丙基-二氢呋喃-2-酮(1)。与目前公开的路线相比,该工艺操作简便,原料价廉易得,各步收率高,适合工业化生产。A new synthetic process of(R)-4-propyl-dihydrofuran-2-one(1), which is the key intermediate of Brivaracetam was reported. Taking valeraldehyde and glyoxylic acid as the starting material,5-hydroxy-4-propylfuran-2(5 H)-one was synthesized by the reaction of valeraldehyde and glyoxylic acid in the presence of morpholine. Then 4-propyl-2-furanone was obtained by removing the hydroxyl at the 5 position with sodium borohydride. Finally, the target compound(R)-4-propyl-dihydrofuran-2-one(1)was obtained by asymmetric reduction in the presence of chiral phosphine ligand s-binap. Compared with the reported route, this synthetic process was simple to operate, higher yield, with low cost and easy availability of raw materials and suitable for industrial production.

关 键 词：布瓦西坦 不对称还原 (R)-4-丙基-二氢呋喃-2-酮 合成 

分 类 号：TQ245[化学工程—有机化工]