Triethylamine → Ethyl 1-(3,3,3-triphenylpropionyl)-4-(4-chlorophenyl)-4-piperidinecarboxylate

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Reaction Steps

A solution of 3.3 parts of 3,3,3-triphenylpropionic acid in 108 parts of dry benzene is treated with 1.8 parts of thionyl chloride. The mixture is refluxed for 2 hours before it is cooled and volatile material is removed under reduced pressure. The residue is dissolved in 88 parts of dry benzene and the solvent is removed again under reduced pressure to again give a residual oil. This is again dissolved in 88 parts of dry benzene and a solution of 2.9 parts of 4-(4-chlorophenyl)-4-piperidinecarboxylic acid ethyl ester and 1.1 part of triethylamine in 27 parts of dry benzene is added at 15°-25° C with stirring. The mixture is then allowed to stand for 16 hours before it is washed successively with dilute hydrochloric acid, water, and dilute aqueous potassium carbonate solution. It is then dried over sodium sulfate and the solvent is evaporated under reduced pressure to leave a residual gum. Upon trituration with pentane the gum solidifies and it is filtered, washed with pentane and air dried to give 1-(3,3,3-triphenylpropionyl)-4-(4-chlorophenyl)-4-piperidinecarboxylic acid ethyl ester melting at about 95°-98° C. 3.8 Patts of this compound is continuously extracted into a suspension of 1.1 part of lithium aluminum hydride in ether with stirring at reflux under nitrogen over a period of one hour. Stirring is continued for an additional 50 minutes and the mixture is decomposed by the successive addition of 1.1 part of water, 0.8 part of 20% aqueous sodium hydroxide solution and 3.9 parts of water. The mixture is filtered and the inorganic material is extracted woth ether. The combined ether solutions are concentrated and diluted with pentane. The solid material which forms is separated by filtration, washed with a mixture of ether and pentane, and dried under reduced pressure to give 1-(3,3,3-triphenylpropyl)-4-(4-chlorophenyl)-4-piperidinemethanol melting at about 156.5°-157.5° C and having the following structural formula ##STR23##

Provenance & Evidence