4-broMo-2-(2-Methoxyethoxy)pyridine

Synthesis

1. 2-Methoxyethanol (0.820 mL, 10.39 mmol) was dissolved in anhydrous THF (30 mL) under nitrogen protection, sodium hydride (60% w/w, 0.416 g, 10.39 mmol) was added slowly and stirred at room temperature for 15 min. 2. 4-bromo-2-chloropyridine (0.577 mL, 5.20 mmol) was added to the above mixture and the reaction was stirred at room temperature overnight. 3. 2-methoxyethanol (0.410 mL, 5.19 mmol) was dissolved in 1,2-dimethoxyethane (10 mL), sodium hydride (60% w/w, 0.208 g, 5.19 mmol) was added and stirred under nitrogen for 15 minutes at room temperature, then the mixture was added to the main reaction system and stirred at room temperature for 3 days. 4. After the reaction was completed, the reaction was quenched by adding water (40 mL), the organic phase was extracted with ethyl acetate, the combined organic phases were washed with saturated brine, dried over hydrophobic filter membrane and concentrated under reduced pressure. 5. The residue was purified by silica gel column chromatography with the eluent being cyclohexane/ethyl acetate (0-20% gradient), and the fraction containing the target product was collected and concentrated under reduced pressure to give 4-bromo-2-(2-methoxyethoxy)pyridine (314 mg, 1.353 mmol, 26.0% yield) as a colorless liquid. 6. 6. The product was analyzed by LCMS (2 min, formic acid): retention time Rt = 0.93 min, molecular ion peak MH+ = 232/234.

References

[1] Patent: WO2014/78257, 2014, A1. Location in patent: Page/Page column 117
[2] Patent: WO2014/140077, 2014, A1. Location in patent: Page/Page column 48