The unique chemical properties of dicyclopropylamine (DCPA) 1 render its synthesis a challenge for process chemists despite its structural simplicity. Chemical instability and high aqueous solubility further complicate the process for DCPA’s preparation, isolation, and purification. In this note we describe the development of three strategies for the synthesis of DCPA 1, all of which provide material with excellent purity profiles (>99 GC area %). Our final route provides significant improvements in terms of cost-efficiency, safety, scalability, and impurity content. Highlights of this strategy include two chemo-selective, Pd-catalyzed, deallylation reactions and an efficient reductive amination protocol. To circumvent the chemical instability of DCPA 1, an innovative isolation procedure was developed which reliably reduced the amount of Pd residue to less than 20 ppm. Following this protocol, impurities such as N-propylcyclopropyl-, mono-cyclopropyl-, and N-ethyl-cyclopropylamines (3, 4, and 17) were minimized to 0.06, not detectable, and 0.02%, respectively.

中文翻译：

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可扩展，高效的二环丙胺盐酸盐制备方法的发展

尽管二环丙胺（DCPA）1的结构简单，但其独特的化学性质使其对工艺化学家来说是一个挑战。化学不稳定性和高水溶性使DCPA的制备，分离和纯化过程进一步复杂化。在本说明中，我们描述了DCPA 1合成的三种策略的开发，所有这些策略均提供了具有出色纯度（> 99 GC面积％）的材料。我们的最终路线将在成本效益，安全性，可扩展性和杂质含量方面进行重大改进。该策略的重点包括两个化学选择性，Pd催化的脱铝反应和有效的还原胺化方案。规避DCPA 1的化学不稳定性，开发了一种创新的分离程序，该程序可将Pd残留量可靠地减少到小于20 ppm。以下这个协议中，杂质如Ñ -propylcyclopropyl-，单-环丙基，和Ñ乙基环丙基胺（3，4和17）被最小化到0.06，而不是检测的，和0.02％之间。