The present work introduced one synthetic method for the medicine intermediate of anamorelin. 3-piperidine ethyl formate was firstly synthesized with 3-pipecolinic acid and ethanol as raw materials through esterification reaction. Then the addition reaction the 3-piperidine ethyl formate with di-tert-butyl pyrocarbonate was conducted under the alkaline condition. The 1-tert-butoxycarbonyl-3-benzyl-3-formic acid piperidine was obtained through hydrolysis with lithium hydroxide hydrate. Finally,the target product was purified via a resolution by employing R-(+)-α-methylbenzylamine as resolving agent. The compounds were characterized by 1H nuclear magnetic resonance spectroscopy and mass spectroscopy. The process optimization results found that the sodium carbonate demonstrated excellent catalytic performance for the reaction. The yield was highest with 1∶4∶4 mole ration of 1-tert-butyloxycarbonyl-3-benzyl-3-ethyl formate peridine/lithium hydroxide hydrate/ethanol and with sodium carbonate as alkali. The present synthetic method is suitable in industry application with its simple operation and high yield.%以3-哌啶甲酸和乙醇为原料酯化生成3-哌啶甲酸乙酯,在碱性条件下与二碳酸二叔丁酯加成,经氢氧化锂水合物水解得到1-叔丁氧羰基-3-苄基-3-甲酸哌啶,通过R-(+)-α-甲基苄胺的手性拆分得目标产物,利用核磁共振氢谱和质谱对其结构进行了表征.并对催化剂及合成工艺进行了优化,结果表明,碳酸钠催化效率最高;1-叔丁氧羰基-3-苄基-3-甲酸乙酯哌啶、氢氧化锂水合物和乙醇的投料质量比为1∶4∶4时,目标产物收率最大.该合成工艺简单、高效,适合放大生产.
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