INTERMEDIATE COMPOUND FOR SYNTHESIZING PHARMACEUTICAL AGENT AND PRODUCTION METHOD THEREOF

摘要

A production method of an optically active 2-{4-(5-substituted-oxadiazolyl) phenyl}morpholine which is useful as an intermediate for synthesizing a pharmaceutical agent is provided and the method comprises the following steps 1) to 4): 1) reacting a bromophenylmorpholine with a hexacyanoferrate(II) or a hydrate thereof at a temperature of from 110°C to 140°C in a reaction mixture comprising a Na2CO3, an organophosphorus compound, and a palladium catalyst in a polar aprotic solvent alone or combination of a polar aprotic solvent and other polar aprotic solvent or hydrocarbon solvent to give a cyanophenylmorpholine; 2) reacting the cyanophenylmorpholine with hydroxylamine or hydroxylamine hydrochloride at a temperature of from 10°C to 40°C in an aprotic polar solvent to give a hydroxylamine derivative; 3) reacting the hydroxylamine derivative with an acylation reagent selected from the group consisting of aliphatic acyl halides, aromatic acyl halides, aliphatic acyl anhydrides and aromatic acyl anhydrides; and 4) keeping the mixture obtained after step 3) at a temperature of from 60°C to 140°C to give a 2-{4-(5-substituted-oxadiazolyl) phenyl}morpholine.