A Facile and Practical Synthesis of (-)-tasimelteon

Abstract

An efficient and practical route for the synthesis of (-)-tasimelteon from 2,3-bis(2-hydroxyethyl)phenol has been developed. The product was prepared in seven steps in overall 16.4% yield using highly stereoselective cyclopropanation reaction of the intermediate as the key step.

An Improved Synthesis of the Triethylene Glycol-Substituted 4-(N-Methyl-N-Boc-Amino)Styrylpyridine

“…Our initial strategy to prepare 3 from 22 consisted of two reactions, β-elimination and then N -methylation. Generally, β-elimination of the tosyl group was carried out in THF with t -BuOK as the base to prepare Boc-protected vinylaniline ( 2 ). , However, as shown in Scheme , the products were affected by the equivalent of t -BuOK. When 1–4 equiv of t -BuOK was screened, besides target compound 2 , a substituted byproduct dimer ( 2a ) and trimer ( 2b ) were also observed through intermolecular substitution; interestingly, 5 equiv of t -BuOK was required for a complete conversion from 22 to 2 for over 2 h. The optimization process is detailed in Table .…”