We describe herein the significant rate-enhancing effect of employing potassium pivalate as a base in a Miyaura borylation. The manufacturing route to verinurad currently employs a Suzuki-Miyaura cross-coupling, requiring cryogenic conditions to generate the boronic acid coupling partner. This process has manufacturability challenges including those associated with low temperature operations and thus an alternative Miyaura borylation approach is described. High throughput screening was employed to investigate the effects of various carboxylate bases and their corresponding counterions on reactivity. Our results highlight potassium pivalate as producing exceptional rate acceleration. To the best of our knowledge this base has not previously been reported for use in Miyaura borylations. Diethanolamine transesterification is also reported as a facile and robust boronate isolation protocol. Successful application of this diethanolamine boronate ester in downstream cross-coupling chemistry has demonstrated the potential for this new route in commercial manufacture of verinurad.

我们在本文中描述了在宫浦硼化中使用新戊酸钾作为碱的显着的增速作用。Verinurad的生产路线目前采用Suzuki-Miyaura交叉偶联，需要低温条件才能生成硼酸偶联伴侣。该工艺具有可制造性的挑战，包括与低温操作有关的挑战，因此，描述了替代的宫浦硼化方法。高通量筛选用于研究各种羧酸盐碱及其相应的抗衡离子对反应性的影响。我们的结果突出了新戊酸钾产生了异常的速率加速。据我们所知，该碱先前尚未报道过可用于宫浦硼酸化反应。还报道了二乙醇胺酯交换是一种简便而稳健的硼酸酯分离方案。该二乙醇胺硼酸酯在下游交叉偶联化学中的成功应用证明了这种新途径在verinurad商业生产中的潜力。