ASYMMETRIC CATALYTIC REDUCTION OF OXCARBAZEPINE

摘要

A process for preparing (S)-(+)- 10,11 -dihydro-10-hydroxy-5H- dibenz/b,f/azepine-5-carboxamide or (R)-(-)-10,l l-dihydro-10-hydroxy-5H- dibenz/b,f/azepine-5-carboxamide, by reduction of oxcarbazepine in the presence of a catalyst and a hydride source is disclosed. The catalyst is prepared from a combination of [RuX₂ (L)]₂ wherein X is chlorine, bromine or iodine, and L is an aryl or aryl-aliphatic ligand, with a ligand of formula (A) or formula (B): wherein R¹ is chosen from C_1-6 alkoxy and C_1-6 alkyl, n is a number from 0 to 5, and when n is a number from 2 to 5, R¹ can be the same or different, and R² is alkyl, substituted alkyl, aryl, substituted aryl, alkaryl or substituted alkaryl. The hydride source is either NR³R⁴R⁵ and formic acid, [R³R⁴R⁵NH][OOCH] and optionally formic acid, or [M][OOCH]_x and formic acid, wherein R³, R⁴ and R⁵ are C_1-6 alkyl, M is an alkali metal or alkaline earth metal and x is 1 or 2. A pH from 6.5 to 8 is maintained during the process.