In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 67567-26-4 as follows. Computed Properties of C6H4BrF2N
10 kg of 4-bromo-2,6-difluoroaniline (48.08 mol) and 67 L of toluene were charged into a reactor under nitrogen atmosphere and stirred at 20 C. until complete dissolution. 1.67 kg of Pd(PPh3)4 (1.44 mol) were charged and stirred for 10 min. 48 L of a 20 wt. % aqueous solution of Na2CO3 were then charged, followed by the addition of a solution of 3-methoxyboronic acid (8.77 kg, 57.7 mol) in methanol (32 L) over 20 minutes. The mixture was heated at 72 C. for 4 hours and then cooled to 20 C.2) Purification of 3,5-difluoro-3′-methoxybiphenyl-4-amine2.1. A solution of 123 L of a 10% aqueous solution of Na2CO3, 1.5 L of a 25 wt. % aqueous solution of ammonia and 2.0 kg of a filtration resin (Dicalite) were charged to the reactor and the mixture stirred for 5 minutes. The mixture was recirculated through a filter until clarification of the liquors (35 min) and charged into a reactor. 60 L of isopropyl acetate were added and the mixture was stirred for 10 minutes and the phases (A1+O1) were allowed to separate. The aqueous phase (A1) was transferred to a different reactor and 60 L of isopropyl acetate were charged. The mixture was stirred and the phases (A2+O2) were allowed to separate. Both organic phases (O1+O2) were charged into a reactor and 108 L of a 10 wt. % aqueous solution of Na2CO3 were added. The mixture was stirred and the phases (A3+O3) were allowed to separate. The organic phase (O3) was stirred with 108 L of a 10 wt. % aqueous solution of Na2CO3 and the phases (A4+O4) were allowed to separate. The organic phase (O4) was stirred with 100 L demineralised water and the phases (A5+O5) were allowed to separate. The organic phase (O5) was filtered over a filtration resin (Dicalite) in a filter and charged in to a reactor.2.2. Distillation: The organic phase (O5) was distilled during 2 hours under reduced pressure (approx. 750 mm Hg) keeping the distilled mixture at temperature below 65 C.3) Preparation of the Aminium Salt (Step b)The distillation residue was dissolved in 100 L of isopropyl acetate, the mixture was cooled to 0-5 C. and 4.2 L of a 35 wt. % aqueous solution of HCl were added drop-wise until the pH was lower than 2. The aminium salt precipitated as a white solid from the dark brown coloured solution. The slurry was stirred for 2 hours at 0-5 C., filtered and the cake washed twice with 50 L of previously cooled isopropyl acetate. The cake was pulled dry under reduced pressure. 3,5-difluoro-3′-methoxybiphenyl-4-aminium chloride was isolated as beige solid. The weight of the wet-cake was 13.83 kg, equivalent to 10.25 kg of dry product (37.73 mol) which corresponds to a yield of 78.5%.
According to the analysis of related databases, 67567-26-4, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Boix Bernardini, Maria Carmen; US2012/245359; (2012); A1;,
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