An Efficient Method for the Synthesis of 2-Methyl-1-substituted-phenyl-2-propylamines

作者：Zhu Lanping; Zhao Shuai; Cang Zhipeng; Zhou Andi; Chen Xin^*

来源：Chinese Journal of Organic Chemistry, 2018, 38(7): 1695-1702.

DOI：10.6023/cjoc201801029

• 2-methyl-1-substituted-phenyl-2-propylamine
• beta(2) adrenoceptor agonist
• Curtius rearrangement
• synthesis

2-Methyl-1-substituted-phenyl-2-propylamines are key intermediates for synthesizing the beta(2) adrenoceptor agonists. A series of 2-methyl-1-substituted-phenyl-2-propylamines have been synthesized starting from substituted benzyl chlorides. Isobutyronitrile was alkylated with benzyl chloride, and the resulting 2-methyl-1-aryl-2-butylcynide was hydrolyzed to give the corresponding acid. Curtius rearrangement of the acid and catalytic hydrolgenation of the resulting Cbz-protected amine afforded the title compound. The method is simple and safe to operate, the raw materials are readily available and the overall yields are satisfactory. This method is suitable for the synthesis of 2-methyl-2-(2-methylphenyl)-phenyl-2-propylamine and various kinds of derivatives.

• 出版日期2018-7-25
• 单位常州大学