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刘为中, 何广卫, 王银虎, 何建勋, 王奎. 1-(4-甲基苄基)-2-甲基-八氢异喹啉盐酸盐的合成[J]. 中国药科大学学报, 2016, 47(5): 548-550. DOI: 10.11665/j.issn.1000-5048.20160507
引用本文: 刘为中, 何广卫, 王银虎, 何建勋, 王奎. 1-(4-甲基苄基)-2-甲基-八氢异喹啉盐酸盐的合成[J]. 中国药科大学学报, 2016, 47(5): 548-550. DOI: 10.11665/j.issn.1000-5048.20160507
LIU Weizhong, HE Guangwei, WANG Yinhu, HE Jianxun, WANG Kui. Synthesis of 1-(4-methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride[J]. Journal of China Pharmaceutical University, 2016, 47(5): 548-550. DOI: 10.11665/j.issn.1000-5048.20160507
Citation: LIU Weizhong, HE Guangwei, WANG Yinhu, HE Jianxun, WANG Kui. Synthesis of 1-(4-methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride[J]. Journal of China Pharmaceutical University, 2016, 47(5): 548-550. DOI: 10.11665/j.issn.1000-5048.20160507

1-(4-甲基苄基)-2-甲基-八氢异喹啉盐酸盐的合成

Synthesis of 1-(4-methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride

  • 摘要: 化合物1-(4-甲基苄基)-2-甲基-八氢异喹啉盐酸盐( 1 )是制备新型镇咳药磷酸二甲啡烷的关键中间体。对化合物 1 的合成工艺进行研究,以4-甲基苯乙酸为原料,采用氯化亚砜氯代制得4-甲基苯乙酰氯,再与2-环己烯基乙胺反应,再经环化、还原、N-甲基化和成盐酸盐纯化得到目标产物 1 ,总收率约54%,纯度大于98%。该工艺具有原料易得、操作简便、产率和纯度高、成本低等优点,适合工业化生产。

     

    Abstract: 1-(4-Methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride( 1 )is the key intermediate to prepare a new type of antitussives agent phosphate dimemorfan. 4-methyl-phenylacetic acid as a raw materials, was chlorinated with thionyl chloride to obtain 4-methyl-phenylacetyl chloride, followed by reaction with 2-cyclohexenyl amine, then cyclization, reduction, methylation and salt formation by HCl were taken out to give the desired product 1 . The total yield is 54%, and the purity is greater than 98%. This synthetic process is characterized with available raw materials, simple in operation with high yield and purity, and suitable for large-scale production.

     

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