Patent ID: 8148527
Filing Date: 2012-04-03
Classification: C07B,C07D

Abstract:
1. A process for resolution of racemic 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline with R-naproxen comprising: (a) treating a solution of the racemic octabasc 1-(4-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline in a suitable solvent with solid R-naproxen or a solution thereof in a suitable solvent, (b) collecting the crystallized salt of (−) 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline with R-naproxen, optionally purifying it by recrystallisation and reserving the mother liquors for recovery of unreacted racemic 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline, (+) 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline and excess of R-naproxen, if any, (c) decomposing the salt as obtained in step (b) above with an alkaline reagent, in the presence of an immiscible organic solvent in which the liberated (−) 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline is soluble, separating the liquid mixture into aqueous and organic solvent phases, reserving the aqueous phase for recovery of R-naproxen; and (d) recovering the free (−) 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline from the organic solvent phase as obtained in step (c) above by removing the solvent, or optionally using the organic solvent phase directly to synthesize dextromethorphan.