|Keywords||4-Methoxy-3-(3-morpholinopropoxy)benzonitrile Gefitinib Synthetic|
Objective4-Methoxy-3-(3-morpholinopropoxy)benzonitrile is a kind of importantpharmaceutical intermediates, can be used to the preparation of the treatmentkinase inhibitors antitumor drugs--Gefitinib.Explore4-methoxy-3-(3-morpholinopropoxy)benzonitrile synthesis process, choose high yield processsimple and easy method, through the test to determine the best synthesisprocess, provide basic research for industrialized production.MethodsOn the basis of the report The Research of4-methoxy-3-(3-morpholinopropoxy) benzonitrile synthesis, we investigated and explored thesynthetic process. This experiment used3-hydroxy-4-methoxy benzeneformaldehyde as starting materials, one step method is adopted to transfer3-hydroxy-4-methoxy benzene formaldehyde into stable cyano3-hydroxy-4-methoxy cyanobenzene and then in the DMF containing potassium carbonate,condensate the compound with N-(3-propyl chloride) morpholine to get targetcompounds4-methoxy-3-(3-morpholine-4-c oxygen radicals)cyanobenzene. Do single factor experiment with the feeding ratio of variousintermediates, reaction temperature and reaction time, choosing the bestreaction conditions, improve the reaction yield, and through improvements onpost-processing simplified the operation. By determining the melting point,analyzing infrared imaging and nuclear magnetism and related structural characterization to confirm the structure of target compounds.ResultsThrough the experiment determined the optimum synthetic route forsynthesis of target compounds, the titled compound was synthesized from3-hydroxy-4-methoxybenzaldehyde. The formyl group was transformed tocyano group via the reaction with hydroxylammonium sulfate in the presence ofsodium formate in formic acid, then the corresponding intermediate reacted withN-(3-chloropropyl) morpholine, the total yield was up to87.5%.The reaction inthe studies and analysis of factors affecting the yield of various intermediates,simplify the operation, improve the yield, safe and reliable, and is more suitablefor industrial production.Confirmed by the analysis of test structure.ConclusionsWith3-hydroxy-4-methoxy benzene, formaldehyde as raw material, forthe target compounds identified a simple synthetic route, and to optimize thesynthesis conditions, the total yield reached87.5%.The whole route do simplecheap raw materials, mild reaction conditions and purification providesexperimental basis for the industrialized production.