2,6-Dibromo-3-methoxypyridine

5.41 A mixture of 2, 6-dibromopyridin-3-ol (4.9 g, 19 mmol), potassium carbonate (2.4 g, 17 mmol), and iodomethane (4.1 mL, 66 mmol) in DMSO (8 mL) was heated at 70 °C for 1.5 h in a sealed tube. The reaction mixture was then cooled to ambient temperature and poured into water. Excess methyl iodide was removed in vacuo, and the resulting mixture was extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting orange solid was recrystallized from hot MeOH (20 mL), and the collected crystals were sequentially triturated with MeOH (2×) and hexanes, then dried in vacuo to give brown crystals (1.7 g). The mother liquor was subsequently concentrated in vacuo and chromatographically purified (silica gel, 0–30percent EtOAc/hexanes) to afford additional product (1.66 g), which was combined with the crystalline material to provide 2, 6-dibromo-3-methoxypyridine (3.36 g, 13 mmol, 65percent yield).[0089] Bromine (1.62 mL, 63.09 mmole) was slowly added dropwise to 25 mL of 20 percent sodium hydroxide (NaOH)aqueous solution at 0°C and the mixture was stirred at 0 °C for 15 min. Then, 3-hydroxypyridine (I) (2.0 g, 21.03 mmole)dissolved in 20 percent sodium hydroxide (NaOH) aqueous solution was slowly added dropwise thereto at 0 °C, and themixture was stirred at 0 °C for 2 hours and then at room temperature for 12 hours. The mixture was filtered to removefloating matter and to the resulting solution was slowly added dropwise 2N hydrochloric acid (HCl) to adjust pH to 1∼2.The resulting solid was filtered and dried to provide a white solid. The solid was dissolved in 60 ml of acetone andpotassium carbonate (K2CO3) (2.64 g, 19.13 mmol) and methaneiodide (CH3I) (893.03 mL, 14.34 mmole) were addeddropwise thereto and the solution was stirred with reflux for 3 hrs. The resulting solution was evaporated under reducedpressure to concentrate, diluted with ethylacetate (EA), and washed with water. The washed organic solvent was driedover anhydrous magnesium sulfate (MgSO4), filtered, and then evaporated under reduced pressure to concentrate. Theresulting residue was isolated and purified by silica gel column chromatography (n-Hex/EA = 5/1) to give the title compound(1.04 g, 19 percent).1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.4 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 3.91 (s, 3H).

Molecular Weight:266.92
XLogP3:2.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:266.87174
Monoisotopic Mass:264.87379
Topological Polar Surface Area:22.1
Heavy Atom Count:10
Complexity:112
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes