Transition-Metal-Free Synthesis of a Densely Functionalized Benzodioxole Intermediate toward Lotiglipron

A decagram-scale preparation of the key intermediate (+/-)-2-(4-bromo-2-methylbenzo[d][1,3]dioxol-2-yl)-5-chloropyridine is described. Key steps involve a double nucleophilic substitution of 3-bromocatechol with methyl 2,2-dichloropropanoate, use of a Weinreb amide to facilitate the formation of a ketone from a carboxylic acid, and de novo construction of a substituted chloropyridine from a vinamidinium salt. Process developments enabled isolation of multigram quantities of final product in 34% yield after 5 steps and no chromatography.