GB629196A - Piperidine derivatives - Google Patents

Abstract

Piperidine derivatives of the general formula <FORM:0629196/IV (b)/1> where R is a cyclohexyl or aryl group, R1 is a branched or non-branched alkyl group and R11 is hydrogen or a methyl group, are prepared by reacting the corresponding 1-alkyl-piperidone-(4) with an aryl-lithium compound in an inert solvent or diluent and acylating the addition product, said acylation being carried out after hydrolysis followed by hydrogenation in the case where a phenyl lithium compound is used and a cyclohexyl derivative is desired. The reaction with the aryl lithium compound takes place in inert solvents or diluents such as ether, benzene, cyclohexane, dioxane, isopropyl ether or pyridine. The acylation is conveniently carried out by reaction with an acyl halide or acid anhydride such as the chlorides or anhydrides of acetic or propionic acid in an inert solvent such as acetone or benzene; and acid binding agent such as pyridine or potassium carbonate may be present, or sulphuric acid and sodium acetate may be added. Hydrogenation to convert the phenyl group " R " into a cyclohexyl group is carried out by treatment with hydrogen, preferably under pressure in the presence of a hydrogenation catalyst, such as platinum, in a solvent such as water, methanol, ethanol, isopropanol, dioxane or ethyl acetate. The piperidine derivatives may be converted into their salts with organic or inorganic acids such as tartaric, maleic, citric, sulphuric, sulphonic or the hydrohalic acids. In examples: (1) 1-isopropyl-4-piperidone is added to phenyl lithium in benzol, the product is treated with propionic anhydride, and hydrochloric acid is added to give the hydrochloride of 1-isopropyl-4-phenyl-4-propionoxy-piperidine, which is converted to the free base by treatment with 1-isopropyl-4-piperidone and the resulting 1-isopropyl-4-phenyl-4-lithiumoxy-piperidine is decomposed with dilute hydrchloric acid to give 1-isopropyl-4-phenyl-4-hydroxy-piperidine which is converted to the hydrochloride, catalytically reduced to 1-isopropyl-4-cyclohexyl-4-hydroxypiperidine hydrochloride and finally treated with propionic anhydride to give 1-isopropyl-4-cyclohexyl - 4 - propionoxy - piperidine hydrochloride; and (3) by using 1 : 3-dimethyl-4-piperidone in place of 1-isopropyl-4-piperidone in the process of (2) there is obtained 1 : 3-dimethyl - 4 - cyclohexyl - 4 - propionoxy piperidine hydrochloride. Aryl-lithium compounds are prepared by reacting lithium metal with aromatic halogeno compounds such as bromobenzene and bromonaphthalene.