2-羟甲基-3-甲基-4-(2,2,2-三氟乙氧基)吡啶的合成  

Synthesis of 2-Hydroxymethyl-3-methyl-4-(2,2,2-trifluoethoxy)pyridine

作　　者：程杰兵 洪家春 赵军 陈英奇[1,2] 张玲玲[1,2] 

机构地区：[1]浙江新三和医药化工股份有限公司,浙江上虞312369 [2]浙江大学化学工程与生物工程学院,浙江杭州310027

出　　处：《中国医药工业杂志》2015年第8期815-816,836,共3页Chinese Journal of Pharmaceuticals

摘　　要：2,3-二甲基-4-硝基吡啶-1-氧化物以碳酸钾和氢氧化钾为混合碱,三氟乙醇为溶剂和反应试剂经亲核取代制得2,3-二甲基-4-(2,2,2-三氟乙氧基)吡啶-1-氧化物,然后在乙酐作用下经重排得3-甲基-2-(乙酰氧基)甲基-4-(2,2,2-三氟乙氧基)吡啶,粗品减压蒸馏纯化,酯交换得2-羟甲基-3-甲基-4-(2,2,2-三氟乙氧基)吡啶,总收率71%,改进后工艺操作简单,适合工业化生产。2-Hydroxymethyl-3-methy1-4-（2,2,2-trifluoethoxy）pyridine was synthesized from 2,3-dimethyl- 4-nitropyridine-l-oxide via nucleophilic substitution with potassium carbonate and potassium hydroxide as mixed alkali, trifluoroethanol as solvent and reagent to give 2,3-dimethy1-4-（2,2,2-trifluoroethoxy）pyridine-1-oxide, which was subjected to rearrangement in the presence of acetic anhydride to obtain crude 3-methyl-2-acetoxymethy1-4-（2,2,2- trifluoroethoxy） pyridine, followed by purification and transesterification with an overall yield of 71%. The improved process had the advantages of simple operation and suitable for industrialized production.

关 键 词：兰索拉唑 抗溃疡药 2-羟甲基-3-甲基-4-(2 2 2-三氟乙氧基)吡啶 中间体 合成 

分 类 号：R975.6[医药卫生—药品] O626.32[医药卫生—药学]