A new and improved synthetic route to an intermediate in the synthesis of the phosphinate ester GSK2248761A is described. In the key step, we describe the first process-scale example of a palladium-catalyzed phosphorus–carbon coupling to give the entire backbone of GSK2248761A in one telescoped stage in 65% average yield on a 68 kg scale. This unusual chemistry enabled the route to be reduced from six chemistry stages to four and eliminated a number of environmentally unfriendly reagents and solvents.

中文翻译：

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非核苷逆转录酶抑制剂GSK2248761A（IDX-899）的生产路线的开发和规模扩大：先进的关键手性中间体的合成

描述了合成次膦酸酯GSK2248761A的中间体的新的和改进的合成途径。在关键步骤中，我们描述了钯催化的磷-碳偶联的第一个工艺规模示例，该阶段可在一个伸缩阶段将GSK2248761A的整个主链以68 kg的平均产率达到65％。这种非同寻常的化学反应使路线从六个化学阶段减少到四个，并消除了许多对环境不利的试剂和溶剂。