Ethanol → 5,5-Dimethoxypiperidin-2-one

Participants

Reaction Steps

Piperidine-2,5-dione (A) described in a literature (J. Am. Chem. Soc., 80, 3717 (1958)) is allowed to react with a lower monoalcohol such as methanol or ethanol, or a with a diol such as ethylene glycol in the presence of an acid catalyst or dehydrating agent, and then the product is treated with an orthoester in the presence of an acid catalyst to obtain 5,5-dimethoxy-2-piperidone (B) whose carbonyl group at the 5-position is protected as an acetal. 5,5-Dimethoxy-2-piperidone (B) is subjected to hydrogen/deuterium exchange reaction using a deuterated compound in the presence of a base to obtain 3,3-dideutero-5,5-dimethoxy-2-piperidone (C), and then the resulting product is subjected to acidic hydrolysis to obtain 2,2-dideutero-5-aminolevulinic acid as a corresponding acid salt.

Provenance & Evidence