Flow Process for Production of Crisaborole Using Organolithium Chemistry with Control over Impurity Formation.

ABSTRACT: Crisaborole, a distinctive boron-containing phosphodiesterase inhibitor, is used for the treatment of atopic dermatitis and eczema in adults and children. The development process for crisaborole involves organolithiation through a Br/Li exchange at -78 °C in batch mode. A continuous flow chemistry process was successfully developed for the synthesis of the key boronate intermediate of crisaborole, enabling efficient mixing, impurity control, and improved yield. The flow approach reduced the residence time dramatically from 1800 s in batch mode to just 1.5 s, and while elevating the temperature from -78 to -60 °C, it maintained precise control over impurity formation and achieved a significant improvement in overall yield. The boronate intermediate was subsequently subjected to one-pot THP

SUBMITTER: Bohara CS 

PROVIDER: S-EPMC12658708 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature