N-(4-甲氧基甲基哌啶-4-基)-N-苯基丙酰胺盐酸盐的合成

Synthesis of N-(4-Methoxymethylpiperidin-4-yl)-N-phenylpropionamide Hydrochloride

1-苄基-4-哌啶酮、苯胺和三甲基氰基硅烷反应制得1-苄基-4-苯胺基-4-氰基哌啶,依次经浓硫酸和氢氧化钾水解、乙酯化、还原及甲基化成醚得1-苄基-4-苯胺基-4-甲氧基甲基哌啶,再经丙酰化、还原脱苄等反应得到阿芬太尼和舒芬太尼的中间体N-(4-甲氧基甲基哌啶-4-基)-N-苯基丙酰胺盐酸盐,总收率约25%(以1-苄基-4-哌啶酮计)。

N-（4-Methoxymethylpiperidin-4-yl）-N-phenylpropionamide, the intermediate of alfentanil and sufentanil, was synthesized from 1-benzyl-4-piperidone, aniline and trimethylsilyl cyanide by reaction to give 1-benzyl-4-phenylamino-4-cyanopiperidine, which was subjected to successively hydrolysis with concentrated sulfuric acid and potassium hydroxide, esterification, reduction and etherification to afford 1-benzyl-4-phenylamino-4- methoxymethylpiperidine, followed by acylation and debenzylation with an overall yield of about 25 %.