Research On Ethy1 5-(4-tert-butoxycarbony1 Piperazin-1-y1) Benzofuran-2-carboxylate

There were many procedures to synthesize ethyl 5-(4-tert-butoxycarbonyl piperazin-1-yl) benzofuran-2-carboxylate, among them, from 5-nitrosalicylaldehyde as starting material via four steps of reactions, i.e.,5-nitrosalicylaldehyde reacted first with ethyl chloroacetate following ring-closure to form ethyl 5-nitrobenzofuran-2-carboxylat. It was reduced into ethyl 5-amino benzofuran-2-carboxylat by catalytic hydrogenation. The latter reacted with bis-2-chloroethyl ammonium chloride to afford ethyl 5-(piperazin-1-yl) benzofuran-2-carboxylate, which reacted with Boc anhydride to give ethyl 5-(4-tert-butoxycarbonyl piperazin-1-yl) benzofuran-2-carboxylate.Due to the cost of production of 5-nitrosalicylaldehyde was too high and not friendly-environment, as well as the yield of ring-closure reaction was too low in the above procedure, we improved the procedure. Afterwards, we further made a pilot plant research on it. During the process, we set up a series of testing method for controlling the reactions.In order to reduce the cost of ethyl 5-amino benzofuran-2-carboxylat, we designed a new synthetic method, i.e., by coupling aniline diazonium salt with salicylaldehyde to get ethyl 2-hydroxy-5-(phenyldiazenyl)benzaldehyde, which reacted with ethyl chloroacetate following ring-closure to afford ethyl 5-phenylazo-benzofuran-2-carboxylate, the latter was reduced to ethyl 5-aminobenzofuran-2-carboxylate in the presence of Pb/C in the hydrogen. During the process, we found that ethyl 5-phenylazo-benzofuran-2-carboxylate possessed cis/trans isomerization in methanol, irradiated by light.