6-甲氧基-2-(4-甲氧苯基)苯并[b]噻吩及其异构体的合成研究

Studies on the synthesis of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene and its isomers

目的合成盐酸雷洛昔芬关键中间体 6 甲氧基 2 (4 甲氧苯基 )苯并 [b]噻吩。方法以 4 甲氧基苯乙酮为原料 ,经溴代、硫醚化先制得α (3 甲氧苯硫基 ) 4 甲氧基苯乙酮 ,再在多聚磷酸(PPA)的催化下 ,经环合及重排制得目标产物。结果与结论从目标产物母液中分离得到 3个异构体 ,它们的化学结构根据高分辨质谱、核磁共振氢谱与红外光谱测试数据确认。改用甲磺酸为催化剂 ,可提高目标产物的收率。

Aim To synthesize 6-methoxy-2-(4-methoxyphenyl)benzothiophene which is an important intermediate for synthesis of raloxifene hydrochloride.Method The target compound was synthesized through bromination and thioetherification from 4-methoxyacetophenone as a starting material.Then polyphosphoric acid(PPA) was used as a catalyst for the cyclization-rearrangement reaction.Results and Conclusion Three isomers accompanied by the target compound were isolated from the mother liquor and their chemical structures were confirmed by IR, 1H-NMR and HRMS.After using methanesulfonic acid as a catalyst instead of PPA,the yield of the target compound was increased in this improved synthesis.