Reference of 1157938-97-0, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 1157938-97-0 name is 1-(2,5-Difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
A 2-neck flask was charged with zinc (5.8 g, 89 mmol, 2.0 eq.) under a nitrogen atmosphere and anhydrous THF (101 mL) and then trimethylsilylchloride (TMSC1, 1.12 mL) were added. The resulting suspension was stirred at room temperature for 30 minutes and then cooled to 0 C. Subsequently, ethyl-2-bromopropionate (5.8 mL, 8.1 g, 44.7 mmol, 1.0 eq.) was dosed to the suspension in a drop wise fashion over 30 minutes. The reaction mixture was stirred for an additional 15 minutes and then filtered under a nitrogen atmosphere into a Schlenk vessel to remove residual zinc. Ketone III (Ri = F, 1.0 g, 4.5 mmol, 1.0 eq.) was charged into a Schlenk vessel and anhydrous THF (10 mL) was added under a nitrogen atmosphere. To the resulting solution was added 20 mL of the previously prepared stock solution of Reformatsky reagent (vide supra, 8.36 mmol, 1.9 eq.) in a dropwise fashion over 30 minutes at room temperature while stirring. After completion of the addition the resulting reaction mixture was stirred under a nitrogen atmosphere for 36 hours (clear solution). GC-analysis showed that the ester I (Ri = F) had formed with 80% conversion based on ketone III (Ri = F) and a d.e. of 60% in favor of the desired RR/SS diastereomer. The reaction mixture was concentrated in vacuo to a volume of 10 mL after which w-heptane was added until formation of a solid was observed. The resulting suspension was stirred for 16 hours after which the solid was isolated through filtration. The solid was then dissolved in a mixture of aqueous HC1 (pH = 1) and ethyl acetate resulting in a clear biphasic system. The phases were separated and the aqueous layer was extracted with ethyl acetate (2x). The combined organic layers were washed with water and brine, dried (Na2S04), filtered and concentrated in vacuo to give racemic RR/SS ester I (Ri = F) as a light yellow solid with > 99% d.e. as determined by GC.
At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(2,5-Difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone, and friends who are interested can also refer to it.
Reference:
Patent; BASILEA PHARMACEUTICA AG; VAN SUMMEREN, Ruben; VAESSEN, Harrie; MINK, Daniel; WASER, Mario; WO2014/23623; (2014); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics