Synthesis
1. benzyl alcohol (4.60 g, 42.6 mmol) was slowly added dropwise to a stirred suspension of sodium hydride (60% mineral oil dispersion, 1.70 g, 42.5 mmol) in dimethylformamide (DMF, 50 mL) under dry conditions.
2. the reaction mixture was heated to 60 °C and stirred at this temperature for 1 h to ensure complete deprotonation.
3. 3,5-dibromopyridine (10.0 g, 42.2 mmol) was dissolved in dimethylformamide (DMF, 20 mL) and this solution was subsequently added to the above reaction mixture.
4. The reaction system was warmed to 80 °C and the reaction was continued with stirring for 2 hours to complete the nucleophilic substitution reaction.
5. Upon completion of the reaction, the reaction mixture was cooled to room temperature and subsequently separated by extraction with ethyl acetate and water.
6. The organic layer was separated and dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product.
7. The crude product was purified by fast column chromatography to afford the target compound 3-benzyloxy-5-bromopyridine (4.75 g, 43% yield).
8. Mass spectrometry (MS) analysis showed the following: m/z calculated value (M + H) + 265, measured value 265, as expected.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 12, p. 3150 - 3155
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 2, p. 717 - 724
[3] Patent: US2013/184313, 2013, A1. Location in patent: Paragraph 1099; 1100
[4] Tetrahedron, 2011, vol. 67, # 26, p. 4767 - 4773
[5] Tetrahedron, 2001, vol. 57, # 20, p. 4447 - 4454
