Synthesis of 1-(2-Ethoxyethyl)-4-(2- (2,2-dimethyl-4-hydroxytetrahydropyranyl)ethynyl)-4-hydroxypiperidine and his diacetate
The aim of the study was to develop simple and affordable methods of synthesis and to search for new effective analgesics with the least side effects among compounds containing piperidine ring in their structure. We used the reaction of condensation of 2,2-dimethyl-4-ethynyltetrahydropyran-4-one with piperidone in order to obtain asymmetric acetylene glycols. The pyran cycle is part of the structure of a number of natural compounds with biological activity. The interaction of ketone (I) with ethynylcarbinol (II) was carried out in an ether medium. In this case, an excess of carbinol was taken, since part of it underwent the Favorsky reverse reaction with the formation of 2,2-dimethyltetrahydropyran-4-one (III). The reaction proceeded slowly, resulting in a mixture ofproducts. After the ketone disappeared from the reaction medium and the reaction mixture was treated (removing excess carbinol and other volatile products under vacuum), glycol oil was released, from which crystalline hydrochloride was obtained. By heating in chloroform with an excess of acetyl chloride, glycol (III) diacetate was obtained as an oil, from which the crystalline salt could not be obtained. Acetylation of glycol with acetyl chloride in acetic anhydride at room temperature leads to the mono acyl derivative (IV). The structure of the synthesized compounds was confirmed using IR, IH and I3C NMR spectra. High analgesic activity of glycol (III), which does not contain in position 4 the piperidine ring of traditional pharmacophore groups (ester or aromatic substituent), was detected.