An unexpected Hoffmann elimination during the alkylation of dihydrotetrabenazine

Dihydrotetrabenazine (DTBZ) is the major pharmacologically active form of tetrabenazine (TBZ), which was approved by FDA for the treatment of chorea associated with Huntington's disease (HD). An unexpected Hoffmann elimination was observed during the treatment of DTBZ with sodium hydrogen and alkyl halides, leading to the formation of both eliminated products (major) and hydroxyl-alkylated products (minor).