Copper-mediated etherification of arenes with alkoxysilanes directed by an (2-aminophenyl)pyrazole group

An efficient copper-mediated etherification of inert C-H bonds of (hetero)arenes with reagent-amounts of alkoxysilanes and alkanols has been developed using (2-aminophenyl)pyrazole (2-APP) as a removable directing group. The reaction is scalable, rapidly proceeds under an open atmosphere, and tolerates diverse functional groups to provide alkyl aryl ethers in high yields (up to 87%). As an application, the formal synthesis of anti-emetic drug metoclopramide is accomplished.