Robust and Scalable Synthesis of Soai Aldehydes via Improved Barbier‐type Halogen–lithium Exchange

A robust synthesis of Soai-type pyrimidine aldehydes proceeds in good to high yields by controlled formation and quenching a lithiated intermediate. The alkyne-substituted bromopyrimidine, furnished Sonogashira cross-coupling, underwent Barbier-type halogen-lithium exchange form transient pyrimidinyl lithium species. rate n-BuLi addition was optimized better synchronize with the ethyl formate, order achieve consistently 2-alkylpyrimdinecarboxaldehydes for use autocatalysis or as functionalized synthons.