Study On The Synthesis Process Of 2-(5-ethyl-2-pyridyl)ethanol

Pioglitazone hydrochloride is a new type of insulin sensitization agent, which is effective on the treatment of non insulin-dependent diabetes mellitus.2-(5-Ethyl-2-pyridyl)ethanol is a key intermediate in synthesis of pioglitazone hydrochloride, therefore, it is very important to study the synthesis process of2-(5-ethyl-2-pyridyl)ethanol.At first, 5-ethyl-2-methylpyridine was obtained from aldehyde-ammonia condensation method. The effects of starting materials and catalysts, molar ratio of raw materials, reaction temperature and reaction time on the synthesis of5-ethyl-2-methylpyridine were investigated. The yield reached 70% under the optimal reaction conditions, which were molar of paraldehyde : ammonium hydroxide : acetic acid being 1:5.3:1.3, reaction temperature 200 ℃, reaction time 2.5 hours and the reaction pressure 2.3 MPa.The obtained 5-ethyl-2-methylpyridine was reacted with 37% aqueous formaldehyde solution to give the target product 2-(5-ethyl-2-pyridyl)ethanol. The optimal reaction condition were obtained through a series experiments, which were molar ratio of5-ethyl-2-methylpyridine to formaldehyde being 2:1, reaction temperature 160℃, reaction time 3 hours and reaction pressure 0.6 MPa. During the process the un-reacted5-ethyl-2-methylpyridine was recovered by distillation under vacuum and directly subjected to the next run. The overall yield of 2-(5-ethyl-2-pyridyl)ethanol reached 66.8%.