Study on the industrial synthetic process of rosiglitazone
This article aims to study the synthetic process of rosiglitazone,solve the scale-up problems of technical process,and obtain a suitable synthetic process for the industrialization of rosiglitazone.2-Chloropyridine and 2-methylaminoethanol were used as starting materials to undergo a substitution reaction to generate 2-[N-methyl-N-(2-pyridyl)amino]ethanol(2).Under the condition of potassium hydroxide as an acid binding agent,compound 2 underwent an etherification reaction with 4-fluorobenzaldehyde to generate 4-[2-(methyl-2-pyridylamino)ethoxy]benzaldehyde(3).Under the catalysis of piperidine,compound 3 underment condensation reaction with 2,4-thiazolidinedione to generate 5-{4-[2-(methyl-2-pyridylamino)ethoxy]phenylmethylene}-2,4-thiazolidinedione(4).Under the catalytic conditions of cobalt chloride hexahydrate and dimethylglyoxime succinate,compound 4 underwent a reduction reaction with sodium borohydride to obtain the crude product of rosiglitazone.The crude product of 1 was prepared into a sodium salt in an anhydrous ethanol and sodium hydroxide system,which was then dissociated into the final target product of rosiglitazone(1)through acetic acid aqueous solution.This synthetic process solves various problems in the large-scale production of rosiglitazone.It has certain practical significance.
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