文摘
An efficient and robust process for the asymmetric hydrogenation of a key intermediate of Montelukast using the highly efficient and selective chiral spiro catalyst Ir/SpiroPAP is reported. The developed process was conducted at mild reaction temperature (30 °C) under a hydrogen pressure of 20 atm with low catalyst loading (S/C = 30?000) and afforded the desired chiral alcohol intermediate in 99.5% ee. This process currently has been carried out at 30 kg scale. The process-related impurities (impurities I–V) were also identified, synthesized, and characterized by LC-MS and NMR techniques.