盐酸左米那普仑的合成

发布时间：2019-07-26 17:12

【摘要】：以苯乙腈为起始原料,在氨基钠作用下与(R)-环氧氯丙烷反应后,经水解、分子内环合得(1S,5R)-1-苯基-3-氧杂二环[3,1,0]己烷-2-酮,在三氯化铝作用下与二乙胺反应得(1S,2R)-N,N-二乙基-2-羟甲基-1-苯基环丙烷-1-甲酰胺,再经氯代、盖布瑞尔反应、氨解,最后与盐酸成盐得盐酸左米那普仑,总收率25.5%(以苯乙腈计)。该工艺条件温和、操作简便,适合工业化生产。
[Abstract]:Using phenylacetonitrile as starting material, after reaction with (R)-epichlorohydrin in the action of sodium amino acid, (1S, 5R)-1-phenyl-3-oxacyclohexane-2-one was synthesized by intramolecular cyclization, and reacted with diethylamine in the action of aluminum trichloride to (1s, 2-hydroxymethyl-1-phenylcyclopropane-1-formamide), and then reacted with diethylamine in the presence of aluminum trichloride to give (1S, 2-hydroxymethyl-1-phenylcyclopropane-1-formamide), and then reacted with diethylamine under the action of aluminum trichloride to (1S, 2hydroxymethyl-1-phenylcyclopropane-1-formamide), and then reacted with diethylamine in the presence of aluminum trichloride. Levminapron hydrochloric acid was obtained by ammonia hydrolysis and salt formation with hydrochloric acid in an overall yield of 25.5% (based on phenylnitrile). The process conditions are mild, the operation is simple, and it is suitable for industrial production.
【作者单位】：河北科技大学化学与制药工程学院;中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室;青岛黄海制药有限责任公司;
【分类号】：R914.5

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