Synthesis of new analogues of 1- [3-Chlorophenyl] -1Methy1-2- Pheny1-2 [2-Pyridine] Ethanol and ethyl 2- [4-Chlorophenoxy] -2Methyl-propionate [Clofibrate]

ABSTRACT

This investigation deals with the synthesis of certain new benzylpyridine derivatives which are structurally related to the hypocholesteremic agents, benzylpyridines and the hypolipidemic agent, clofibrate. The new compounds, l-alkyl-1-[4-substained phenyl]-2- phenyl-2-[2-pyridyl] ethanols 6a-c, were synthesized by the interaction between 2-benzylpyridine and the appropriate ketone in presence of n-BuLi. Compound 6c was obtained in a poor yield which may be attributed to the steric effect of the relatively bulky starting material 4c. Phenyl-2-pyridyl-3,4,5-trimethoxybenzoyl methane 8 was obtained in a very low yield when 2-benzylpyridine was reacted with methyl 3,4,5-trimothoxybenzoate in presence of KNH2 in liquid NH3. The same procedure failed to yield ketones 12 and 13. Also, trials to synthesize these ketones by the direct interaction between the corresponding acid chloride and 2-benzylpyridine in presence of n-BuLi gave unexpected products of uncertain structures. It is of interest that n-BuLi affected the condensation very successfully, instead of KNH2 between ethyl 3-dimethylamino benzoate or phenoxyacetic acids-esters and 2-benzylpyridine to yield 3-dimethyl-aminobenzoylphenyl-[2-pyridyl] methane 12 and substituted phenoxyacetylphenyl-[2-pyridyl] methonal was obtained for the first time as a low melting point solid. Several other unsuccessful trails were reported and discussed