Development of an improved and scalable process for 2-(5-ethylpyridin-2-yl) ethan-1-ol: Solvent-free reaction and recycling of the starting material 5-ethyl-2-picoline
The main objective of this exercise was to develop a more efficient process for 2-(5-ethylpyridin-2-yl)ethan-1-ol (1), which is the key intermediate in the synthesis of pioglitazone hydrochloride. This process not only features the yield improvement of (1) by optimizing reaction variables in solvent-free conditions but also highlights improving the mass efficiency of 5-ethyl-2-picoline (2), thereby reducing the effluent load per kilogram of the intermediate.