Synthesis of ethyl 4,5-bis(diethoxyphosphorylmethyl)-3-furoate

Abstract

Preparative procedure for 4,5-bis(diethoxyphosphorylmethyl)-3-furoate from 4-chloromethyl-3-furoate is developed. It includes substitution of chlorine with iodine, phosphorylation by means of the Arbuzov reaction, chloromethylation of 4-(diethoxyphosphorylmethyl)-3-furoate in the position 5 of the furan ring, substitution of chlorine with iodine in the obtained chloromethyl derivative, and repeated phosphorylation with triethyl phosphite. It was found that ethyl 4-(diethoxyphosphorylmethyl)-5(chloromethyl)-3-furoate reacts with sodium diethyl phosphite by two pathways. Besides usual nucleophilic substitution leading to phosphonate, transfer of the reaction center in the position 2 of the furan ring takes place. The ambident diethylphosphite anion in this case reacts at the oxygen to give tertiary phosphite. The latter is oxidized with the air oxygen to form ethyl 2-(diethoxyphosphoryloxy)-4-(diethoxyphosphorylmethyl)-5-methyl-3-furoate. Unlike that analogous iodomethyl phosphonate is phosphorylated selectively under the conditions of the Arbuzov reaction.