Large Scale Synthesis of Chiral (3Z,5Z)‑2,7-Dihydro‑1H‑azepine-Derived Hamari Ligand for General Asymmetric Synthesis of Tailor-Made Amino Acids

An advanced process for large scale (500 g) preparation of a (3Z,5Z)-2,7-dihydro-1H-azepine-derived chiral tridentate ligand (Hamari ligand), widely used for asymmetric synthesis of tailor-made α-amino acids via the corresponding glycine Schiff base Ni­(II) complex, is disclosed. The process includes amidation, bis-alkylation, and precipitation/purification of the target compound by TFA as a counterion.