Piperazine → Ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]piperazinecarboxylate

Participants

Reaction Steps

As depicted in Scheme 5, the known piperazine intermediate, for example, ethyl 1-piperazinecarboxylate (2000-2001 Aldrich Chemical catalog, pg 795), was reacted with the known methyl halide, for example 4-(2-pyridyloxy)phenylmethyl chloride (WO 97/26252) under basic conditions in an appropriate solvent, affording the corresponding ethyl ester, ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]piperazinecarboxylate (AA). Intermediate (AA) was then oxidized with, for example 30% hydrogen peroxide, providing the corresponding 4-oxide, ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]-4-oxypiperazinecarboxylate (BB), which in turn was decarboxylated with a strong aqueous base, providing the corresponding free piperazine 4-oxide, for example 2-[4-(4-oxypiperazin-1-ylmethyl)phenoxy]pyridine (CC).

Provenance & Evidence