硫酸沙丁胺醇的合成研究Ⅰ

Studies on Synthesis of Salbutamol Sulfate Ⅰ

以水杨醛与叔丁胺为起始原料，经缩合、酯化、Ｆｒｉｅｓ重排三步一锅反应制成２－氯－１－｛［（１，１－二甲基乙基）亚胺基甲基］－４－羟基苯基｝－乙基酮（４）．再经缩合、水解、成盐三步一锅反应转化成５－｛［（１，１－二甲基乙基）胺基］乙酰基｝－２－羟基苯甲醛盐酸盐（５），再经甲醇钠中和、催化转移氢化还原、成盐即得硫酸沙丁胺醇（１），总收率约５０％。

An improved synthetic technique of salbutamol sulfate was established. 2-chloro-1-[3-[[(1,1-bimethylethyl)imino]methyl]-4-hydroxyphenyl]-ethanone(4) was obtained via condensation, esterification and Fries rearrangment from salicyl aldehyde and tertbutylamine in a one-pot procedure.(4) was subjected to condensation, hydrolysis and salt formation in a onepot procedure to afford 5-[[(1,1-dimethylethl)amino]acetyl]-2-hydroxy benzaldehyde hydrochloride(5).(5) was subsequently converted to salbutamol sulfate via neutraiization with sodium methoxide, catalytic transfer, hydrogenation and salt formation. The overall yield is about 50%.