A new synthesis of 1-arylpiperidin-4-ols

Abstract

1,5-Dichloropentan-3-ol (8), which is readily prepared from the corresponding ketone (7), reacts with 2-fluoro-, 4-methyl-, 2-chloro-, 3-chloro-, 4-chloro-, and 3-chloro-4-methyl-anilines in the presence of potassium carbonate and sodium iodide in dimethylformamide at 100 °C to give 1-(2-fluorophenyl)-, 1-(4-tolyl)-, 1-(2-chlorophenyl)-, 1-(3-chlorophenyl)-, 1-(4-chlorophenyl)-, and 1-(3-chloro-4-tolyl)piperidin-4-ols, respectively. The (2-fluorophenyl)-, (4-tolyl)-, and (4-chlorophenyl)-piperidin-4ols are converted into the corresponding 1-arylpiperidin-4-ones. 1-(2-Fluorophenyl)piperidin-4-one (10; R¹= F, R²= R³= H) is converted into its dimethyl acetal (12) and thence into the enol ether (13).