Background and overview of preparation and application of 2,6-dichloropyridine-4-boronic acid
2,6-Dichloropyridinium trifluoromethylbenzene boric acid-4-boronic acid can be used as a pharmaceutical synthesis intermediate. It can use 2,6-dichloro-4-iodopyridine as the reaction raw material, in n-butyllithium prepared by reaction. 2,6-Dichloropyridine-4-boronic acid can be used in Suzuki reaction to synthesize the pharmaceutical intermediate 2,6-dichloro-4-[5-(trifluoromethyl)pyridin-2-yl]pyridine.
Preparation
Under nitrogen protection, n-BuLi (3mL, 2.5M hexane solution, 1.50 equivalents) was added dropwise to 2,6-dichloro-4-iodopyridine (1.40g, 5.112mmol, 1.00 equiv) in tetrahydrofuran (20 mL). The resulting solution was stirred at -78°C for 30 min. Trimethylborate (580 mg, 5.582 mmol, 1.10 equiv) was added at -78°C and the reaction was stirred at -78°C for 1 h. The resulting solution was stirred at room temperature for an additional 12 h, then quenched with 1.6 g of pinacol and AcOH (0.6 mL). The solid was filtered off and the liquid was concentrated in vacuo to give the title compound 2,6-dichloropyridine-4-boronic acid (1 g, crude) as a yellow solid.
Preparation and application of 2,6-dichloropyridine-4-boronic acid
2,6-Dichloropyridin-4-boronic acid can be used to prepare compound 2,6-dichloro-4-[5-(trifluoromethyl)pyridin-2-yl]pyridine. The specific reaction process is as follows: Under nitrogen protection, 2-bromo-5-(trifluoromethyl)pyridine (800.00mg, 3.54mmol, 1.00 equivalent), 2,6-dichloropyridine-4-boronic acid (1g, 5.21mmol, 1.00 equivalent), Pd(dppf)Cl2.CH2Cl2 (290mg, 0.36mmol, 0.10 equivalent) and potassium carbonate (1.96g, 14.18mmol , 4.00 eq.) in 1,4-dioxane (40 mL)/water (2 mL) was stirred at 120 °C for 12 h. The resulting solution was diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with ethyl acetate/petroleum ether (1:100) to give 2,6-dichloro-4-[5-(trifluoromethyl)pyridin-2-yl]pyridine (680mg, 66%), as a white solid.
References
[1] CN105612153-Substituted heterocyclic sulfonamide compounds used as TRPA1 modulators
