The reaction optimization of an alkylation to enable the production of the penultimate intermediate of an HIV-attachment inhibitor candidate is described. To address the challenges associated with the reactivity and stability of di-tert-butyl (chloromethyl) phosphate (2), and the poor solubility and reactivity of the starting BMS-626529-Li salt (1), strategic selection of Et₄NI and 325 mesh K₂CO₃ as additives, and wet CH₃CN as solvent were required. An aqueous workup protocol was also developed to selectively remove an undesired N-6 alkylation isomer. The final processing conditions resulted in the isolation of the penultimate compound 3 in 70% yield with high purity.

中文翻译：

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HIV附着抑制剂BMS-663068的制备。第8部分。膦氧甲基前药部分的安装

描述了烷基化的反应优化，以使得能够产生HIV-附着抑制剂候选物的倒数第二个中间体。为了解决与反应性和二-稳定性相关的挑战叔丁基（氯甲基）酯（2），以及差的溶解性和反应性起始BMS-626529-Li盐（1），等的战略选择₄ NI和需要325目K ₂ CO ₃作为添加剂，并且需要湿CH ₃ CN作为溶剂。还开发了水性处理方案以选择性除去不希望的N-6烷基化异构体。最终加工条件导致分离出倒数第二个化合物3 收率高达70％，纯度高。