A Convenient Route to 1-Alkyl-5-trifluoromethyl-1,2,3-triazole-4-carboxylic Acids Employing a Diazo Transfer Reaction

• Published in: European journal of organic chemistry Vol. 2013; no. 14; pp. 2891 - 2897
• Main Authors: Iminov, Rustam T., Mashkov, Alexander V., Chalyk, Bohdan A., Mykhailiuk, Pavel K., Tverdokhlebov, Anton V., Tolmachev, Andrey A., Volovenko, Yulian M., Shishkin, Oleg V., Shishkina, Svetlana V.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-05-2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Acids; Amines; Azides; Fluorine; Medicinal chemistry; Nitrogen heterocycles; Synthetic methods
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201300030

The reaction of ethyl 3‐(alkylamino)‐4,4,4‐trifluoro‐but‐2‐enoates with mesyl azide in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) gave ethyl 1‐alkyl‐5‐trifluoromethyl‐1,2,3‐triazole‐4‐carboxylates in good yields. Further hydrolysis of the ester group afforded the title compounds on a multigram scale.
A multigram‐scale synthesis of 1‐alkyl‐5‐trifluoromethyl‐1,2,3‐triazole‐4‐carboxylic acids has been developed. The triazole ring formation by means of a diazo transfer reaction with mesyl azide was the key step.