G.d. Searle & Company

Gatis Plume

Joseph J Wieczorek

Mike G Scaros

John R Medich

John H Dygos

Kathleen T McLaughlin

Thomas R Kowar

Michael L Prunier

Richard J Salzmann

The present invention relates to a novel process for the preparation of heterocyclic alkylamide derivatives having the following formula: ##STR1## and the pharmaceutically acceptable acid addition salt thereof wherein X represents halo, alkyl having 1 to 6 carbon atoms, hydrido, trifluoromethyl, phenyl, or lower alkoxy having 1 to 6 carbon atoms; Y represents the group --CN or --CONH.sub.2 ; R.sub.2 represents alkyl having 1 to 6 carbon atoms; R.sub.3 represents acetyl, benzoyl, phenacetyl or trifluoroacetyl; m is the integer 1 or 2 and n is an integer from 1 to 3 inclusive; which comprises alkylating an aminoalkanol using a benzaldehyde/aminoalkanol/ketone mixture in the presence of a platinum catalyst to give an alkyl substituted phenylmethylaminoalkanol; halogenating the alkanol using a halogenating agent to give a haloalkyl alkylbenzenemethanamine salt; treating the salt with substituted phenyl piperidinealkanenitrile or substituted phenyl pyrrolidinealkanenitrile in the presence of base and dimethyl sulfoxide to give a substituted phenyl substituted aminoalkyl piperidinealkanenitrile or substituted aminoalkyl pyrrolidinealkanenitrile; hydration of the nitrile to give the corresponding amide; and N-debenzylation of the amide followed by acetylation to give the compounds of formula I wherein Y is --CONH.sub.2.

Process for the preparation of heterocyclic alkylamide derivatives

A process for the resolution of (.+-.)-.alpha.-[2-[acetyl(1-methylethyl)amino]ethyl-.alpha.-(2-chloropheny l)-1-piperidinebutanamide having the following structure ##STR1## into its (+) and (-) enantiomers using camphorsulfonic acid.

Process for the resolution of

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