An Efficient Synthetic Method for the Key Fragment of Lifitegrast: Benzofuran‐6‐carboxylic Acid

Abstract This article presents a simple and efficient method for synthesizing the key fragment of lifitegrast, benzofuran‐6‐carboxylic acid. The synthetic pathway involves two key conversions such as intramolecular cross‐coupling and oxidative dehydrogenation reactions to obtain the target compound. The first key reaction, the cross‐coupling reaction, proceeds smoothly with the use of 1.2 equivalents of zinc dust in a dimethylacetamide medium at 60 ° C. The second key reaction, the oxidative dehydrogenation of dihydrobenzofuran occurs comfortably with the catalytic amount of DDQ along with 6 equivalents of MnO 2 in a chlorbenzene medium to generate the benzofuran moiety in good yield. We also discussed in‐detail about the impurity formation and its control by adjusting the pH, reagent quantity, solvent quality etc. The proposed synthetic route has been scaled up to a multi‐gram scale.The proposed approach offers several advantages, including scalability and cost‐effectiveness by utilizing inexpensive and readily available raw materials.