“一锅三步法”合成苯基-2-吡啶基甲醇

One-pot three-steps method for the synthesis of phenyl-2-pyridyl-methanol

以2-苄基吡啶氮氧化物和三氟乙酸酐为原料,通过"一锅三步法"(串联"酰化、[3,3]σ重排和水解"反应)合成了关键药理活性中间体苯基-2-吡啶基甲醇,并对反应条件进行了优化。结果表明,当n(2-苄基吡啶氮氧化物)∶n(三氟乙酸酐)=1.0∶1.2、N,N-二异丙基乙胺(DIPEA)为碱、甲苯为溶剂,室温反应6 h,经硅胶柱层析分离即可得到苯基-2-吡啶基甲醇,收率为81.0%。产物经1HNMR、13CNMR和HRMS进行结构确证。该反应以原子经济学的理念实现了由2-苄基吡啶氮氧化物到苯基-2-吡啶基甲醇的高效直接转化。

Phenyl-2-pyridinyl-methanol,as a key pharmacological intermediate,was synthesized from 2-benzylpyridine nitrogen-oxide and trifluoroacetic anhydride via one-pot three-steps method(tandem acylation,[3,3]-sigmatropic rearrangement and hydrolysis reaction).The reaction conditions were optimized and the optimal conditions were obtained as follows:n(2-benzylpyridine nitrogen-oxide)∶n(trifluoroacetic anhydride)=1.0∶1.2,N,N-diisopropylethylamine(DIPEA)as base,toluene as solvent,reaction temperature room temperature and reaction time 6 h.Under the above-mentioned conditions,the reaction mixture was purified by silica gel column chromatography and obtained phenyl-2-pyridinylmethanol with a yield of 81.0%.The structures of products were confirmed by 1 HNMR,13CNMR and HRMS.This reaction achieved efficient and direct transformation from 2-benzylpyridine nitrogen-oxide to phenyl-2-pyridyl-methanol by atomic economic theory.