Reaction #3053

Reaction equation

potassium hydroxide

piperidinebutanenitrile

(±)-α-(2-chlorophenyl)-1-piperidinebutanenitrile

bromoacetaldehyde dimethyl acetal

→

(±)-α-(2-chlorophenyl)-α-(2,2-dimethoxyethyl)-1-piperidinebutanenitrile

Solvents

dimethylsulfoxide

Conditions

Procedure

The synthesis outlined in Scheme II comprises (a) reacting commercially available 2-chlorobenzeneacetonitrile with 1-(2-chloroethyl)piperidine in the presence of a base, such as sodium hydroxide, and methyltributylammonium chloride to give (±)-α-(2-chlorophenyl)-1-piperidinebutanenitrile; (b) alkylating the resulting piperidinebutanenitrile with bromoacetaldehyde dimethyl acetal in dimethylsulfoxide (DMSO) in the presence of potassium hydroxide to produce (±)-α-(2-chlorophenyl)-α-(2,2-dimethoxyethyl)-1-piperidinebutanenitrile; (c) hydrolyzing the resulting piperidinebutanenitrile in a solvent such as toluene with hydrochloric acid to produce (±)-α-(2-chlorophenyl)-α-(2-oxoethyl)-1-piperidinebutanenitrile; (d) reacting the resulting piperidinebutanenitrile with isopropylamine in a solvent such as toluene in the presence of potassium carbonate to form an imine substituted piperidinebutanenitrile; (e) reducing the resulting imine substituted piperidinebutanenitrile with sodium borohydride and ethanol to form an amino substituted piperidinebutanenitrile; (f) acetylating the resulting amino substituted piperidinebutanenitrile with acetic anhydride in a solvent such as toluene to produce an acetylated amino substituted piperidinebutanenitrile; (g) hydrolyzing the resulting acetylated amino substituted piperidinebutanenitrile with sulfuric acid to produce an acetylated amino substituted-1-piperidinebutanamide; and (h) isolating the resulting 1-piperidinebutanamide.

Source