Analyzing the synthesis route of 436799-32-5

Adding a certain compound to certain chemical reactions, such as: 436799-32-5, 5-Bromo-2-(trifluoromethyl)pyridine, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, name: 5-Bromo-2-(trifluoromethyl)pyridine, blongs to pyridine-derivatives compound. name: 5-Bromo-2-(trifluoromethyl)pyridine

In a dried 250 mL 3-neck round bottom flask fitted with a stirrer bar, thermometer, and flushed with nitrogen, was placed anhydrous THF (16 mL, Aldrich, inhibitor free) followed by N, N-diisopropylamine (0.895 g, 8.85 mmol, Aldrich, redistilled 99.95% pure). After cooling the stirred solution to -70 0C, n-butyl lithium (3.54 mL of a 2.5M solution in hexanes, 8.85 mmol) was added dropwise, keeping the reaction temperature less than -60 0C. The resulting solution was stirred at -70 0C for a further 10 min, then warmed to -20 0C, before immediately cooling to -90 0C. A solution of 5-bromo-2-(trifluoromethyl)pyridine (2 g, 8.85 mmol) in anhydrous THF (8 mL, Aldrich, inhibitor free) was added dropwise, keeping the reaction temperature less than -85 0C. The resulting orange solution was stirred at -90 0C for 40 min.In a separate dried 250 mL 3-neck round bottom flask fitted with a stirrer bar, thermometer, and flushed with nitrogen, was placed anhydrous THF (5 mL, Aldrich, inhibitor free) followed by methyl iodide (5 mL, 80 mmol). The solution was cooled to -90 0C. To this was added (via cannula) the solution of the pre-formed lithiated pyridine, controlling the rate so as to keep the reaction temperature of the receiving flask less than -80 0C. The resulting dark solution was stirred at -90 0C for a further 15 min (LCMS indicated reaction complete). The reaction was quenched with sat aq. NH4CI solution (50 mL), then allowed to slowly warm to room temperature. Organics were extracted with EtOAc (2 x 50 mL), then the combined organic layers washed with water (50 mL), then brine (50 mL), separated, dried over MgSO4, and then filtered. Concentration in vacuo gave 1.68 g of a brown oil which was purified via short-path vacuum distillation (45-46 0C, ca. 5 mmHg) to give 5-bromo-4-methyl-2- (trifluoromethyl)pyridine 1-2 (0.289 g, 14%) as a yellow oil (>97% pure). MS (M + H)+: 241.8, tR = 2.458 min (method 1 ); 1H NMR (CDCI3) delta 8.74 (1 H, s), 7.56 (1 H, s), 2.50 (3H, s).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,436799-32-5, 5-Bromo-2-(trifluoromethyl)pyridine, and friends who are interested can also refer to it.

Reference:
Patent; NEUROCRINE BIOSCIENCES, INC.; WO2008/124610; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem