Making Complex Chiral Amines by Catalytic Resolution-Racemisation-Recycle (R3-Process)

该项目旨在建立并迅速开发一种令人兴奋的新工艺来制造旋光性胺，该工艺始于当前AZ支持的CASE学生（Blacker/Munday/Kwan）。该方法利用了非对映体晶体分辨率的优势——高选择性、简单稳健和可扩展的工艺、低成本和广泛适用，并克服了主要限制——最高产率为50%，同时存在相关的浪费和成本问题。到目前为止，已经对一系列20和30种手性胺进行了评估，这些手性胺通常产率为80%，产率为95%。我们现在希望通过研究在开发化合物中经常遇到的旋光性b-氨基醇和相关的手性中心来扩大r3工艺的范围。另一个方面是发展对非对映体溶解度的理解，以帮助溶剂选择和预测盐对。该项目解决了阿斯利康博士合作呼吁，开发一种新的更有效的产品分离方法。

This project aims to build-upon and move rapidly to exploit an exciting new process to make optically active amines that started with a current AZ supported CASE studentship (Blacker/Munday/Kwan). The method takes advantage of the benefits of diastereomeric crystal resolution - high selectivity, simple robust and scalable process, low cost and widely applicable, and overcomes the major limitation - maximum 50% yield with associated waste and cost issues. Thus far the scope has been evaluated with a series of 2o and 3o chiral amines, typically made in >80% yield and >95% e.e. We now wish to widen the scope of the R3-Process by researching optically active b-amino alcohols, and related chiral centres, that are frequently encountered in development compounds. A further aspect is to develop an understanding of diastereomer solubility to assist in solvent selection and predict salt pairs. The project addresses the AZ PhD Collaborations Call in developing a new more efficient method of product isolation.