DOI: 10.1055/a-2991-3513 ISSN: 0039-7881
Phthalide-to-Phthalane Strategy for the Synthesis of Citalopram and its Analogues
Hamdi Sanaa, Enzo Eddebbarh, Jerome Thibonnet, Julien PetrignetCitalopram is a widely prescribed racemic selective serotonin reuptake inhibitor (SSRI) and a privileged scaffold for the design analogues. We report new synthetic approaches to citalopram based on 3-arylphthalide. The first route, starting from an easily accessible 6-methoxyphthalide, was successfully elaborated up to a mesylate-citalopram precursor. The second, bromide-based route proved fully productive, delivering citalopram in six steps and 23% overall yield. This strategy was applied to prepare three original citalopram amino-analogues, highlighting the versatility of this synthetic pathway.