Step-1: Synthesis of 5-bromo-3-chloro-2-isobutoxypyridine
To a solution of 5-bromo-3-chloro-2-fluoropyridine (5.0 g, 23.7 mmol) and 2-methylpropan-1-ol (5.28 g, 71.3 mmol) in DMSO (100 mL) was added CS2CO3 (23.0 g, 71.3 mmol). The reaction mixture was heated at 90 °C for 3 hours. After the reaction was completed, the mixture was cooled to room temperature and diluted by adding water (500 mL). The aqueous layer was extracted with ether (2 x 500 mL). The organic extracts were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography (silica gel 100-200 mesh, 0-5% ethyl acetate in hexane solution) to afford the target compound 5-bromo-3-chloro-2-isobutoxypyridine (5.0 g, 86% yield) as a colorless oil.
TLC conditions: 10% hexane solution of ethyl acetate, product Rf value: 0.8.
MS (ESI, cation mode): no ionization peaks were observed.
1H NMR (400MHz, CDCl3) δ 8.06 (d, J = 2.2Hz, 1H), 7.74 (d, J = 2.2Hz, 1H), 4.11 (d, J = 6.7Hz, 2H), 2.12 (dp, J = 13.4,6.7Hz, 1H), 1.03 (d, J = 6.7Hz, 6H).
