[Synthesis]
General procedure for the synthesis of 5-bromo-2-cyclopropylpyridine from 2,5-dibromopyridine and cyclopropylmagnesium bromide: Under argon protection, 0.5 M THF solution (5.5 mL, 2.8 mmol) of 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine was added to 0.5 M cyclopropylmagnesium bromide in a THF solution (5.5 mL, 2.8 mmol). The reaction mixture was stirred at room temperature for 2 h to form a slurry. Subsequently, 2,5-dibromopyridine (0.65 g, 2.8 mmol) and PdCl2-dppf (0.041 g, 0.050 mmol) were added to the slurry in one go. After a few minutes, an exothermic phenomenon was observed and the slurry thickened. After the exotherm subsided, the reaction mixture was continued to be stirred at room temperature overnight. After completion of the reaction, the mixture was poured into saturated sodium bicarbonate solution and extracted with ether. The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated. The residue was redissolved in dichloromethane, filtered through a short silica gel column and washed with dichloromethane. After concentrating the eluate, the residue was dissolved in ether and the aqueous phase was adjusted to alkaline with 2.0 M sodium hydroxide solution and the product was again extracted with ether. The combined ether phases were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 0.28 g (50% yield) of 5-bromo-2-cyclopropylpyridine as a yellow oil.LC-MS m/z 197.9/199.9 (M+1); 1H-NMR (CDCl3) δ 8.48 (d, 1H), 7.63 (dd, 1H), 7.04 (d, 1H), 1.99 (d, 1H). 1H), 1.99 (m, 1H), 1.03-0.98 (m, 4H) ppm. |