2-氯甲基-3,5-二甲基-4-硝基吡啶盐酸盐的合成工艺改进

Improvement on Synthesis of 2-Chloromethyl-3,5- dimethyl-4-nitropyridine Hydrochloride

以2,3,5-三甲基吡啶为原料,研究了抗胃溃疡药物奥美拉唑的关键中间体2-氯甲基-3,5-二甲基-4-硝基吡啶盐酸盐的合成工艺。研究中发现氧化反应以磷钨酸为催化剂,不用溶剂醋酸,可高收率制得吡啶N氧化物,硝化后,改用醋酸酐为重排试剂,再以质量分数为15%的盐酸为水解剂,最后经氯化亚砜氯化可顺利制得标题化合物,五步总收率达70%,并经1HNMR确证了结构。

2-Chloromethyl-3,5-dimethyl-4-nitropyridine hydrochloride, an important intermediate of omeprazole which is a very effective drug for the treatment of gastric ulcer, was prepared by N-oxidation with phosphotungstic acid as catalyst without solvent、nitration、rearrangement with acetic anhydride、hydrolysis in acidic condition and chlorination. The overall yield was over 70% and the molecular structure of the title compound was confirmed by ()~1H NMR.