PROBLEM TO BE SOLVED: To provide a method of producing an optically active substituted polycyclic pyridone derivative having a cap-dependent endonuclease inhibitory activity, and a crystal of the derivative.SOLUTION: The method of producing a compound represented by formula (V) includes: subjecting to coupling reaction of an optically active substituted tricyclic pyridone derivative with a thiepin derivative without reducing an optical purity by changing to a hexyl group from a protective group other than a non-substituted alkyl group such as a benzyl group in an optically active substituted tricyclic pyridine derivative intermediate.SELECTED DRAWING: None【課題】キャップ依存的エンドヌクレアーゼ阻外活性を有する、光学活性な置換された多環性ピリドン誘導体の製造方法およびその結晶の提供。【解決手段】式(V)で示される化合物の製造方法であって、光学活性な置換3環性ピリドン誘導体中間体において、ベンジル基など非置換アルキル以外の保護基からヘキシル基に交換することにより、光学純度を低下させることなく、光学活性な置換3環性ピリドン誘導体とチエピン誘導体とのカップリング反応を進行させる製造方法。【選択図】なし