A new and efficient process to prepare di-tert-butyl (chloromethyl) phosphate, a key compound in the formation of many phosphon-oxymethyl pro-drugs, from chloromethyl chlorosulfate (CMCS) and di-tert-butyl potassium phosphate (DTBPP) is described. To develop a process to this important compound with overall efficiency, an improved synthesis of DTBPP was required. The two-step process to DTBPP starts from PCl₃ and leverages a H₂O₂/catalytic KI mediated oxidation of di-tert-butyl phosphite to provide DTBPP in 81% yield and high purity. In the development of the new process to di-tert-butyl (chloromethyl) phosphate, a comparison to the corresponding tosylate derivative was made. A rational selection of base, phase-transfer catalyst (PTC), and stabilizing additive minimized CMCS decomposition and led to an optimized yield (90% solution yield), improved product purity, and identification of a technique to enable the long-term storage of di-tert-butyl (chloromethyl) phosphate.

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制备磷酸二叔丁基钾和磷酸二叔丁酯（氯甲基）的有效方法的发展

由氯甲基氯硫酸盐（CMCS）和磷酸二叔丁基钾（DTBPP）制备磷酸二叔丁酯（氯甲基）的新方法是一种高效的新方法，磷酸二叔丁酯是许多膦-氧甲基前药形成中的关键化合物。描述。为了开发一种具有重要功效的重要化合物的方法，需要改进DTBPP的合成方法。在两个步骤的过程来从DTBPP开始的PCl ₃和一杠杆ħ ₂ ö ₂ / KI催化介导的二氧化叔丁基酯在81％的产率和高纯度提供DTBPP。在新的发展过程中，以二叔进行了磷酸（氯甲基）丁酯与相应甲苯磺酸酯衍生物的比较。合理选择碱，相转移催化剂（PTC）和稳定化添加剂可最大程度地减少CMCS分解，并导致优化的收率（溶液收率达90％），提高的产品纯度，并确定了能够长期储存二-叔丁基（氯甲基）酯。