biostudies-literatureUnknown15(49)Jia CThis study presents an optimized synthetic pathway for suvorexant and establishes a robust method for the simultaneous determination of residual solvents. The synthesis commenced with chiral precursors, specifically (<i>R</i>)-3-(BOC-amino)butyric acid and <i>N</i>-benzyl glycine ethyl ester, employing a fragment splicing strategy. The target compound was synthesized through a sequence of nucleophilic reactions, BOC deprotection, cyclization, reduction, BOC protection, affinity substitution, and subsequent nucleophilic reactions, thereby circumventing the need for chiral separation. The post-treatment process was refined <i>via</i> recrystallization to yield the active pharmaceutical ingredient (API). For residual solvent analysis, a headspace gas chromatography (HS-GC) method was developeRSC advances41597-41607https://www.ebi.ac.uk/biostudies/studies/S-EPMC12573263biostudies-literatureOptimized synthesis of suvorexant and determination of eight residual solvents by headspace gas chromatography.PMC12573263Liu YWang QJia CShi WZheng AWang XYu ZZhao JfalseOptimized synthesis of suvorexant and determination of eight residual solvents by headspace gas chromatography.This study presents an optimized synthetic pathway for suvorexant and establishes a robust method for the simultaneous determination of residual solvents. The synthesis commenced with chiral precursors, specifically (<i>R</i>)-3-(BOC-amino)butyric acid and <i>N</i>-benzyl glycine ethyl ester, employing a fragment splicing strategy. The target compound was synthesized through a sequence of nucleophilic reactions, BOC deprotection, cyclization, reduction, BOC protection, affinity substitution, and subsequent nucleophilic reactions, thereby circumventing the need for chiral separation. The post-treatment process was refined <i>via</i> recrystallization to yield the active pharmaceutical ingredient (API). For residual solvent analysis, a headspace gas chromatography (HS-GC) method was develope2025-01-01T00:00:00Z2025 Oct2026-06-05T09:44:03.422Z2026-05-15T03:12:01.191ZS-EPMC125732634118102110.1039/d5ra06779k