Volinanserin

Volinanserin (INN) (developmental code name MDL-100,907) is a highly selective 5-HT2A receptor antagonist that is frequently used in scientific research to investigate the function of the 5-HT2A receptor. It was also tested in clinical trials as a potential antipsychotic, antidepressant, and treatment for insomnia but was never marketed.

Synthesis
The protection of Ethyl isonipecotate [1126-09-6] (1) with Boc anhydride gives ethyl n-boc-4-piperidinecarboxylate [142851-03-4] (2). Ester-amide interchange with N-Methoxymethylamine HCl: [6638-79-5] in the presence of CDI coupling agent gives 1-Boc-4-[methoxy(methyl)carbamoyl]piperidine [139290-70-3] (3). Weinreb ketone synthesis occurs upon benzoylation with 1,2-Dimethoxybenzene [91-16-7] (4) to give 1-Boc-4-(3,4-dimethoxybenzoyl)piperidine, [2322526-86-1] CID:139510111 (5). Acid removal of the urethane protecting group gives (3,4-dimethoxyphenyl)-piperidin-4-ylmethanone [742665-98-1] (6). The reduction of the ketone with sodium borohydride leads to (3,4-Dimethoxyphenyl)-piperidin-4-ylmethanol, CID:24261124 (7). Resolution of the alcohol gives (8). Sn2 alkylation of the secondary nitrogen with 4-Fluorophenethyl bromide [332-42-3] (9) completed the synthesis of Volinanserin (10).