An unexpected synthesis and application of ethyl 2,4-bis(chloromethyl)-6-iodoquinoline-3-carboxylate

Abstract

An unexpected and direct synthesis of ethyl 2,4-bis(chloromethyl)-6-iodoquinoline-3-carboxylate (3) from the chlorotrimethylsilane (TMSCl)-promoted Friedlander reaction between 1-(2-amino-5-iodophenyl)ethanone (2) and ethyl 4-chloro-3-oxobutanoate has been disclosed. As a versatile and attractive building block, a synthetic application of the poly-functionalized quinoline 3 in the successive Williamson ether synthesis with various phenols and in situ ester hydrolysis reaction has been achieved and the corresponding 2,4-bis(aroxymethyl)quinoline-3-carboxylic acids (5a-k) were obtained in good yields of 71–86%.