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 1157938-97-0 as follows. category: Triazoles
To a solution of diisoproplylamine (120 g) in dry THF (1500 ml) 1.6 M solution of butyllithium in hexane (730 ml) was slowly added at -40 C. under nitrogen atmosphere. The mixture was allowed to warm up to -20 C. for ca. 10 min, then re-cooled to -78 C. and to this LDA-solution N,N-bis(2,4-dimethoxybenzyl)thiopropionamide (390 g), dissolved in dry THF (500 ml) was slowly added that the reaction temperature did not exceed -40 C. (exothermic reaction, cooling). After addition the mixture was stirred at -40 C. for ca. 1 hr, then at this temperature 1-(2,5-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (223 g), dissolve in dry THF (400 ml), was slowly added, the reaction mixture stirred for another 2 hrs, then within ca. 1 hr warmed up to -20 C. and finally poured on an aqueous phosphate buffer solution (pH 7). The aqueous phase was extracted 3 times with ethylacetate (500 ml) and the combined organic phases dried twice with sodium carbonate, filtered and evaporated under reduced pressure providing 3-(2,5-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)-N,N-bis(2,4-dimethoxybenzyl)thiobutyramide: 590 g (96% yield) as a single diastereomer. This crude material was dissolved at 0 C. under cooling in a mixture of methylenechloride (1000 ml) and triflic acid (150 g) and slowly triethylsilane (500 g) was added within ca. 3 hrs keeping the temperature under 10 C. After the reduction was finished the reaction mixture was poured very slowly on aqueous saturated sodium bicarbonate solution, extracted 3 times with ethylacetate (500 ml), dried with sodium sulphate, filtered and evaporated under reduced pressure providing the crude title compound: 250 g (80% yield). The analytical data were identical with published one for (2R,3R)-enantiomer in U.S. Pat. No. 6,300,353 and WO99/45008.
According to the analysis of related databases, 1157938-97-0, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Carbo-Design LLC; US2011/87030; (2011); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics