1-(四氢吡咯-1-甲基)-1,2,3,4-四氢异喹啉盐酸盐的合成工艺改进

Improvement on the Synthesis of 1-(Pyrrolidin-1-ylmethyl)-1,2,3,4-tetrahydroisoquinoline Hydrochloride

以苯乙胺为原料,经氯乙酰氯酰化、Bischler-Napieralski反应、胺化、还原、成盐制得1-(四氢吡咯-1-甲基)-1,2,3,4-四氢异喹啉盐酸盐(2)。在文献基础上通过用五氧化二磷/三氯氧磷混合脱水剂代替单一的五氧化二磷,通过减少溶剂甲醇及提高亲核试剂四氢吡咯的用量及重结晶替代柱层析的改进,使总收率由27%提高到53%。

1-（Pyrrolidin-1-ylmethyl）-1,2,3,4-tetrahydroisoquinoline is an important intermediate for organic synthesis. A novel process was developed for the synthesis of the title compound in an overall yield of 53% from phenethylamine. Improvements were achieved by using mixture of P2O5/POC13 instead of P205 as the dehydrating agent, less methanol, more tetrahydropyrrole and recrystallization in place of column chromatography for the purification.