Stereoselective preparation of substituted piperidines

A process for preparing a compound of high enantiomeric purity of the formula ##STR16## wherein R.sup.1 is aryl selected from indanyl, phenyl and naphthyl;

• heteroaryl selected from thienyl, furyl, pyridyl and quinolyl;
• and cycloalkyl having 3 to 7 carbon atoms, wherein one of said carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur;
• wherein each of said aryl and heteroaryl groups may optionally be substituted with one or more substituents, and said (C.sub.3 -C.sub.7)cycloalkyl may optionally be substituted with one or two substituents, said substituents being independently selected from chloro, fluoro, bromo, iodo, nitro, (C.sub.1 -C.sub.10)alkyl optionally substituted with from one to three fluoro groups, (C.sub.1 -C.sub.10)alkoxy optionally substituted with from one to three fluoro groups, amino, (C.sub.1 -C.sub.10)alkyl-S--, ##STR17## (C.sub.1 -C.sub.10)alkyl-SO.sub.2 --, phenyl, phenoxy, (C.sub.1 -C.sub.10)alkyl-SO.sub.2 NH--, (C.sub.1 -C.sub.10)alkyl-SO.sub.2 NH--(C.sub.1 -C.sub.10)alkyl--, (C.sub.1 -C.sub.10)alkylamino-di(C.sub.1 -C.sub.10)alkyl--, cyano, hydroxyl, cycloalkoxy having 3 to 7 carbon atoms, (C.sub.1 -C.sub.6)-alkylamino, (C.sub.1 -C.sub.6)dialkylamino, ##STR18## wherein the nitrogen atoms of said amino and (C.sub.1 -C.sub.6)alkylamino groups may optionally be protected with an appropriate protecting group;
• and R.sup.2 is thienyl, benzhydryl, naphthyl or phenyl optionally substituted with from one to three substituents independently selected from chloro, bromo, fluoro, iodo, cycloalkoxy having 3 to 7 carbon atoms, (C.sub.1 -C.sub.10)alkyl optionally substituted with from one to three fluoro groups and (C.sub.1 -C.sub.10)alkoxy optionally substituted with from one to three fluoro groups, comprising reacting a compound of the formula ##STR19## wherein R.sup.2 is defined as above, with either (a) a compound of the formula ##STR20## wherein R.sup.1 is defined as above and X is a leaving group, followed by treatment of the resulting amide with a reducing agent, (b) a compound of the formula R.sup.1 CHO, wherein R.sup.1 is defined as above, in the presence of a reducing agent, or (c) a compound of the formula R.sup.1 CH.sub.2 X, wherein R.sup.1 is defined as above and X is a leaving group.

A process for preparing a compound of the formula ##STR21## wherein R.sup.1 is aryl selected from indanyl, phenyl and naphthyl;

• heteroaryl selected from thienyl, furyl, pyridyl and quinolyl;
• and cycloalkyl having 3 to 7 carbon atoms, wherein one of said carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur;
• wherein each of said aryl and heteroaryl groups may optionally be substituted with one or more substituents, and said (C.sub.3 -C.sub.7)cycloalkyl may optionally be substituted with one or two substituents, said substituents being independently selected from chloro, fluoro, bromo, iodo, nitro, (C.sub.1 -C.sub.10)alkyl optionally substituted with from one to three fluoro groups, (C.sub.1 -C.sub.10)alkoxy optionally substituted with from one to three fluoro groups, amino, (C.sub.1 -C.sub.10)alkyl-S--, ##STR22## (C.sub.1 -C.sub.10)alkyl-SO.sub.2 --, phenyl, phenoxy, (C.sub.1 -C.sub.10)alkyl-SO.sub.2 NH--, (C.sub.1 -C.sub.10)alkyl-SO.sub.2 NH--(C.sub.1 -C.sub.10)alkyl--, (C.sub.1 -C.sub.10)alkylamino-di(C.sub.1 -C.sub.10)alkyl--, cyano, hydroxyl, cycloalkoxy having 3 to 7 carbon atoms, (C.sub.1 -C.sub.6)alkylamino, (C.sub.1 -C.sub.6)dialkylamino, ##STR23## wherein the nitrogen atoms of said amino and (C.sub.1 -C.sub.6) alkylamino groups may optionally be protected with an appropriate protecting group;
• and R.sup.2 is thienyl, benzhydryl, naphthyl or phenyl substituted with from one to three substituents independently selected from chloro, bromo, fluoro, iodo, cycloalkoxy having 3 to 7 carbon atoms, (C.sub.1 -C.sub.10)alkyl optionally substituted with from one to three groups and (C.sub.1 -C.sub.10)alkoxy optionally substituted with from one to three fluoro groups;
• comprising reacting a compound of the formula ##STR24## wherein R.sup.2 is defined as above, with a compound of the formula R.sup.1 CHO, wherein R.sup.1 is defined as above, in the presence of a drying agent or using an apparatus designed to remove azeotropically the water generated, to produce an imine of the formula ##STR25## wherein R.sub.1 and R.sub.2 are defined as above, and reacting the imine with a reducing agent.