Related Products of 42872-83-3,Some common heterocyclic compound, 42872-83-3, name is 2-Bromo-5-methylbenzonitrile, molecular formula is C8H6BrN, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
MethyI-2-(pyrimidin-2-yl)benzonitrile (2); To a 500 mL three neck round bottom flask, equipped with an overhead stirrer, thermocouple and nitrogen inlet and dropped funnel, was charged 2-bromo-5-methylbenzylnitrile1 (20.00 g) and THF (60 mL, 3 V) and was cooled to -15 C. 1.3 M of i-PrMgCI’LiCl (1 10.0 mL, 1.4 equiv) was slowly added at -15 to -12 C. The reaction mixture was stirred at -15 to -12 C for 3.5 h (> 99 A% conversion). 15.45 g of anhydrous ZnCl2 (1.1 equiv, powder) was added to the Grignard reagent at -12 C in one portion. The reaction was exothermic raising the temperature of the reaction mixture to 0 C. The reaction mixture was stirred at -3 to 2 C for 0.5 h and slowly warmed to rt over 0.5 h. The reaction mixture became a homogenous solution and then 2-chloropyrimidine (15.37 g) was added.To a slurry of 1 mol% Pd(OAc)2 (0.229 g), 4 mol% («-Bu)3P (0.826 g or 1.02 mL) in THF (8 mL) was added 2.0 M of BuMgCl (1.02 mL) THF solution to become yellow cloudy solution, The resulting catalyst solution was added to the reaction mixture. The resulting mixture was heated at 55 C for 17 h: (98 A% conversion). The reaction mixture was solvent-switched to isopropyl alcohol (140 mL, total volume) at 40-45 C. Then 5 wt% NH4C1 aqueous solution (70 mL) was added dropwise at 15 to 20 C. The resulting slurry was aged at 10 C for 5 h. The crystalline solid was collected by filtration, rinsed with cold isopropyl alcohol/water (1 : 1, 35 mL), and ^-heptane (30 mL), dried under vacuum with nitrogen sweep and gave desired product2 (17.33 g, 87% isolated yield, 99.5 LCAP purity).HPLC MethodColumn: Zorbax Eclipse Plus CI 8 50 x 4.6 mm, 1.8 muetaiota particle size, Column Temp.: 25 C; Flow Rate: 1.5 mL/min; Detection: 230 nm; Mobile Phase: A: Water 0.1% H3PO4, B: AcetonitrileMobile Phase Program: Time A0 90%5 min 5%6 min 5%6.1 min 90%8 min 90%Compound 2: 3.19 min
The synthetic route of 42872-83-3 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; MERCK SHARP & DOHME CORP.; FENG, Yun Shao; MOSES, Anthony; ZHONG, Yong-Li; WO2012/58129; (2012); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts