Diastereoisomeric esters of 1,2-dimethyl-4-phenylpiperidin-4-ol and related compounds

Abstract

The synthesis of 1,c-2- and 1,t-2-dimethyl-4-phenylpiperidin-r-4-ols and derived esters is reported. Configurations and preferred conformations are assigned on the basis of reactivity of the alcohols towards thionyl chloride and Raney nickel, ¹H n.m.r. characteristics, and the observation of epimeric conjugate acids in cis-derivatives. The stereochemistry of the hydrogenolysis products is confirmed by comparing N-methyl chemical shifts of methiodide derivatives with those calculated from the shielding influence of 2eq- and 2ax-methyl substituents. The hot-plate ED₅₀ values (for mice) of acetate and propionate esters of the piperidinols are reported and compared with those of analogues lacking 2-methyl substituents.