Malonic Acid → [4-Phenyl-1-(3,3,3-triphenylpropyl)piperidin-4-yl]methanol--hydrogen chloride (1/1)

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Reaction Steps

A mixture of 2 parts of triphenylcarbinol and 8 parts of malonic acid are heated at 170° for 31 hours. This mixture is cooled and then dissolved in hot ethanol. 3,3,3-Triphenylpropionic acid, melting at 182°, crystallizes from the ethanol upon cooling. 1 Part of 3,3,3-triphenylpropionic acid is then refluxed with 5 parts of thionyl chloride for 4 hours and the excess thionyl chloride is removed in vacuum to provide the crude 3,3,3-triphenylpropionyl chloride. 9 Parts of this 3,3,3-triphenylpropionyl chloride are then reacted with 27.0 parts of ethyl 4-phenyl-4-piperidinecarboxylate in the presence of 4 parts of triethylamine in benzene. The resulting amide is reduced with 5 parts of lithium aluminum hydride in ether at reflux for 2.5 hours. The reaction mixture is cooled and treated with 15% aqueous sodium hydroxide solution to decompose any unreacted lithium aluminum hydride. The reaction mixture is then filtered and washed with ether. The ether solution is evaporated to give an oil. This oil is then slurried in 10% HCl and extracted with ether. The aqueous phase which contains an insoluble oil is extracted with methylene chloride, and the methylene chloride extract dried over anhydrous sodium sulfate. Evaporation of this methylene chloride solution gives a solid which is taken up in acetone and precipitated with ether to give 1-(3,3,3-triphenylpropyl)-4-(phenyl)-4-piperidinemethanol hydrochloride, melting at about 256°-259° C.

Provenance & Evidence