Synthesis
General procedure for the synthesis of ethyl 2-(3-bromo-2-pyridyl)acetate from 2-methyl-3-bromopyridine and diethyl carbonate: lithium hexamethyldisilazane (436 mL, 0.44 mmol, 1 M hexane solution) was dissolved in anhydrous ether (1 L) under nitrogen protection. 2-Methyl-3-bromopyridine (25.0 g, 0.14 mol) was slowly added and the reaction mixture was stirred at room temperature for 1 hour. Subsequently, diethyl carbonate (26.0 mL, 0.22 mol) was added dropwise and the reaction mixture continued to be stirred overnight. Upon completion of the reaction, the reaction mixture was washed three times with a half-saturated aqueous sodium chloride solution (3 x 250 mL) and the organic phase was dried with anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure and the residue was dissolved in hexane (200 mL). The solution was filtered through a silica gel pad (10 g) and the silica gel pad was rinsed with additional hexane (100 mL). The solvent was again concentrated under reduced pressure to remove the solvent to give the crude product. The crude product was stirred under high vacuum for 1 h to remove volatile impurities, resulting in ethyl 2-(3-bromo-2-pyridyl)acetate (37.7 g) in yellow liquid form. The molecular ion peak [M + H]+ of the product was 244.1 as analyzed by LCMS.
References
[1] Organic Letters, 2016, vol. 18, # 8, p. 1713 - 1715
[2] Synthesis, 1997, # 8, p. 949 - 952
[3] Patent: WO2014/201127, 2014, A2. Location in patent: Paragraph 00567
[4] Patent: WO2016/94710, 2016, A1. Location in patent: Paragraph 0116-0117
