降血脂药Apabetalone的合成新方法

A Novel Synthetic Route for the Hypolipidemic Apabetalone

本研究报道了一条合成apabetalone的新路线。以价廉易得的1-溴-3,5-二甲氧基苯(9)为起始原料,经酰化得2-溴-4,6-二甲氧基苯甲醛(10),经Pinnick氧化得2-溴-4,6-二甲氧基苯甲酸(11),11无需纯化直接成酰胺得2-溴-4,6-二甲氧基苯甲酰胺(12),和4-[2-[(叔丁基二甲基硅)氧]乙氧基]-3,5-二甲基苯甲醛(8)及氨水构成喹唑啉酮环制得apabetalone,纯度99.3%,总收率24.0%(以9计)。本路线反应条件温和,操作简便,其中由11制备apabetalone的方法未见文献报道。

A new synthetic route of apabetalone was reported. 2-Bromo-4,6-dimethoxybenzaldehyde（10） was prepared via acylation from 1-bromo-3,5-dimethoxybenzene（9）, subsequently 10 was subjected to Pinnick oxidation to give 2-bromo-4,6-dimethoxybenzoic acid（11） at room temperature, which was followed by amidation to afford 2-bromo-4,6-dimethoxybenzamide（12）. Finally, the target compound was obtained from a cyclization of 12 and 4-[2-[（tertbutyldimethylsilyl）oxy]ethoxy]-3,5-dimethylbenzaldehyde（8） in ammonia with an overall yield of 24.0%（based on 9）and a purity of 99.3%. The new synthetic route had some advantages, such as mild reaction conditions, simple operation, high yield, which was more feasible for industrial production, and the method for preparing apabetalone from 11 has not yet been reported in literature.