Diethyl Ether → 1-[4-(4-Methylanilino)-1-(2-phenylethyl)piperidin-4-yl]ethan-1-one

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Reaction Steps

To a stirred solution of 17.4 parts of lithium in 140 parts of dry 1,1'-oxybisethane is added dropwise a small amount of a solution of 193.7 parts of iodomethane in 210 parts of dry 1,1'-oxybisethane. After the reaction is started by heating, there are added 420 parts of dry 1,1'-oxybisethane. The remainder of the solution is added dropwise at reflux temperature. Stirring at reflux is continued for 45 minutes. Then there are added portionwise (quickly) 41.8 parts of 4-[(4-methylphenyl)amino]-1-(2-phenylethyl)-4-piperidinecarboxylic acid (exothermic reaction: reflux temperature is maintained). Upon completion, stirring at reflux is continued for one hour. The reaction mixture is cooled in an ice-bath and decomposed by the dropwise addition of 1000 parts of water. The organic layer is separated and discarded. The aqueous phase is extracted with 1,1'-oxybisethane. The extract is dried, filtered and evaporated. The solid residue is crystallized from 2,2'-oxybispropane. The product is filtered off and recrystallized from 2,2'oxybispropane, yielding 26 parts (62.4%) of 1-{4-[(4-methylphenyl)amino]-1-(2-phenylethyl)-4-piperidinyl}ethanone; mp. 133.7° C.

Provenance & Evidence