Efficient and Practical Synthesis of 3′,4′,5′-Trifluoro-[1,1′-biphenyl]-2-amine: A Key Intermediate of Fluxapyroxad

Abstract

An improved and practical method is reported here for accessing 3′,4′,5′-trifluoro-[1,1′-biphenyl]-2-amine (1), a key intermediate for Fluxapyroxad. The overall yield for the preparation of 1 was 73%, with a purity of 99.88%, after a three-step process. More importantly, this process was an improvement in the manufacture of biphenyl compounds by Suzuki−Miyaura coupling, which enabled catalyst loading as low as 0.04 mol %. This method could provide an economic and environmentfriendly process leading to extensive prospects in industrial applications.

Synthesis, Catalytic Activity and Comparative Leaching Studies of Calix[8]arene‐Supported Pd‐NHC Complexes for Suzuki‐Miyaura Cross‐Couplings

“…The coupling between 1,2,3‐trifluoro‐5‐bromo‐benzene and 2‐aminophenylboronic acid leads to the formation of 12 , an advanced synthon towards the antifungal drug Fluxapyroxad [20] . This reaction was also performed successfully with both calixarene‐supported NHC catalysts (Tables 6 and SI‐5).…”

Trace amounts of palladium catalysed the Suzuki–Miyaura reaction of deactivated and hindered aryl chlorides

“…Our research group had reported a practical method for synthesizing the key intermediate of Fluxapyroxad, where 3′,4′,5′-trifluoro-2-nitro-1,1′-biphenyl could be efficiently synthesized through the SMC reaction under standard conditions with a low catalyst loading of 0.04 mol% Pd. 19 However, when proceeding this optimized system to the SMC reaction with deactivated aryl chlorides results in suboptimal performance, achieving only 45% yield (see Table 1, entry 1). Next, we aimed to develop a more efficient catalytic system for SMC reactions of unreactive aryl chlorides at low catalyst loadings, by selecting sterically hindered and 1-chloro-2-methoxybenzene and phenylboronic acid as model substrates and through systematic screening of ligands, bases, solvents, and other factors.…”

Calixarene-supported Pd–NHC complexes as efficient catalysts for scalable Suzuki–Miyaura cross-couplings

“…Furthermore, inspired by a recent report on the synthesis of a key intermediate for the preparation of Fluxapyroxad, a synthetic carboxamide with antifungal properties, 15 the crosscoupling between 5-bromo-1,2,3-trifluorobenzene and (2aminophenyl) boronic acid was evaluated. The reaction implied the use of cat1 with a 1 mol % loading in palladium, and allowed isolation of the target product (eq.…”