Enantioselective synthesis of 2-ethyl-2,3-dihydrobenzofuran carboxylic acid, direct precursor of (+)-efaroxan, from a Baylis–Hillman adduct

We describe herein a new and straightforward enantioselective approach to R-(+)-2-ethyl-2,3-dihydrofuran carboxylic acid, the direct precursor of (+)-efaroxan, an α2 adrenoreceptor antagonist, which is indicated to be used for the treatment of neurodegenerative diseases (Alzheimer and Parkinson), migraine and type II diabetes. Our goal was accomplished using a Baylis–Hillman adduct as starting material. The dihydrobenzofuran acid was obtained in eight steps with an overall yield of 14%.