Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X). This was alkylated with 1-(2-chloroethyl)imidazolinone (XII), (prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII). The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).

In an alternative method, Ullmann arylation of potassium N-(4-fluorophenyl)glycinate (VI) with potassium 2,5-dichlorobenzoate (V) afforded the N,N-diaryl glycine (VII). Cyclization of diacid (VII) in refluxing Ac2O produced the 3-acetoxy indole (VIII). This was then reduced to indole (IV) with NaBH4 in refluxing EtOH.

Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X). This was alkylated with 1-(2-chloroethyl)imidazolinone (XII), (prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII). The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).

In an alternative method, Ullmann arylation of potassium N-(4-fluorophenyl)glycinate (VI) with potassium 2,5-dichlorobenzoate (V) afforded the N,N-diaryl glycine (VII). Cyclization of diacid (VII) in refluxing Ac2O produced the 3-acetoxy indole (VIII). This was then reduced to indole (IV) with NaBH4 in refluxing EtOH.

Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X). This was alkylated with 1-(2-chloroethyl)imidazolinone (XII), (prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII). The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).

Decarbomethoxylation of the known 3-hydroxyindole-2-carboxylate (I) in the presence of magnesium chloride in NMP at 160 C afforded indolinone (II), which was subsequently reduced with NaBH4 to the 3-hydroxy indoline (III). Dehydration of (III) by means of trifluoroacetic acid furnished indole (IV).

In an alternative method, Ullmann arylation of potassium N-(4-fluorophenyl)glycinate (VI) with potassium 2,5-dichlorobenzoate (V) afforded the N,N-diaryl glycine (VII). Cyclization of diacid (VII) in refluxing Ac2O produced the 3-acetoxy indole (VIII). This was then reduced to indole (IV) with NaBH4 in refluxing EtOH.

Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X). This was alkylated with 1-(2-chloroethyl)imidazolinone (XII), (prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII). The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).