PRODUCTION OF (-)-1-BENZYL-4-((5,6-DIMETHOXY-1-INDANON)-2-YL)METHYLPIPERIDINE

• Main Authors: KIYOFUJI NOBUO, KUMOBAYASHI HIDENORI, KAJIMA TAKASHI, SUGIMOTO HACHIRO, ARAKI SHIN, IIMURA YOICHI
• Format: Patent
• Language: English
• Published: 06.07.1992
• Subjects: APPARATUS THEREFOR; CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PERFORMING OPERATIONS; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; THEIR RELEVANT APPARATUS; TRANSPORTING

PURPOSE:To obtain a compound useful as a medicine in ultrahigh optical purity and high yield by asymmetrically hydrogenating a methylpiperidine derivative in the presence of a ruthenium-phosphine complex catalyst. CONSTITUTION:(E)-1-Benzyl-4-[(5,6-dimethoxy-1-indanon)-2-ylidenyl]meth ylpyridine expressed by formula I is hydrogenated in the presence of an optically active ruthenium-phosphine complex catalyst in a solvent such as methylene chloride at 25-75 deg.C under 4-100kg/cm pressure for 24-168hr by passing hydrogen therethrough to afford the objective substance, expressed by formula II, having inhibitory action on acetylcholinesterase and useful as a therapeutic agent for Alzheimer's diseases. At least one or more of compounds expressed by formulas III, IV and V (X us halogen; Y is H, amino, acetylamino, etc.; R is H or lower alkyl; A and Z are ClO4, BF4, etc.; n is 1 or 2) are used as the ruthenium- phosphine complex.