As a result of recent efforts in green solvent selection, methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate, sold under the brand name Rhodiasolv PolarClean, has received considerable scientific and industrial attention as a possible non-toxic replacement for common polar aprotic solvents. However, the multicomponent nature and multi-step synthesis of this solvent remains an obstacle for its more widespread use and niche applications. In this work, a retrosynthetic approach was taken to identify novel shorter synthetic routes in alignment with green chemistry principles. High purity methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate was obtained in novel single-step reactions via two different base-catalysed Michael additions from readily available building blocks. The more advanced synthetic route shows great potential owing to the swift (30 min), solvent-free reaction and catalytic amounts of base (<6.5 mol%). Green metrics analysis, including Atom Economy, Complete E factor, Carbon Intensity and hazard analysis found the new synthesis to be more sustainable than the patented routes. Application of this green solvent was demonstrated for the first time for O- and N-arylation in S_NAr reaction with solvent recovery with similar or superior yields compared to other green solvents. Moreover, broad opportunities for this green solvent in membrane science were identified, where the use of conventional, toxic polar aprotic solvents in large quantities is unavoidable. Important practical solvent properties and parameters such as dielectric constant, solubility parameters, solvent miscibility and NMR residual shifts have been determined to facilitate the uptake of methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate as a green solvent.

中文翻译：

---

迈向更清洁的PolarClean：极性非质子溶剂5-（二甲氨基）-2-甲基-5-氧戊酸甲酯的高效合成和广泛应用

由于最近在绿色溶剂选择方面做出的努力，以Rhodiasolv PolarClean品牌出售的5-（二甲基氨基）-2-甲基-5-氧戊酸甲酯已经受到了相当多的科学和工业关注，作为一种可能的无毒替代品。极性非质子溶剂。然而，该溶剂的多组分性质和多步合成仍然是其更广泛使用和特殊应用的障碍。在这项工作中，采用逆合成方法来识别符合绿色化学原理的新颖的较短合成路线。通过新颖的一步反应，通过以下方法获得了高纯度的5-（二甲氨基）-2-甲基-5-氧戊酸甲酯两种易于使用的结构单元在碱催化下的迈克尔加成反应。由于快速（30分钟），无溶剂反应和碱催化量（<6.5 mol％），更先进的合成路线显示出巨大的潜力。绿色指标分析，包括原子经济，完全E因子，碳强度和危害分析，发现新合成比专利路线更具可持续性。首次证明了这种绿色溶剂在S _N中用于O-和N-芳_{基化的应用}与其他绿色溶剂相比，具有反应回收率的Ar反应具有相似或更高的收率。此外，在膜科学中发现了这种绿色溶剂的广泛机会，在这种情况下，不可避免地大量使用常规的有毒极性非质子溶剂。已经确定了重要的实用溶剂特性和参数，例如介电常数，溶解度参数，溶剂混溶性和NMR残留位移，以促进摄取5-（二甲基氨基）-2-甲基-5-氧戊酸甲酯作为绿色溶剂。