Tetrahydrofuran → 2-Chloro-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

To a −78° C. solution of 2-chloro-3-fluoro-5-iodo-4-methyl-pyridine (498.6 mg; 1.837 mmol) in tetrahydrofuran (6.0 mL; 74 mmol) was added isopropylmagnesium chloride lithium chloride complex (1.3 mol/L) in THF (5.8 mL; 7.5 mmol). The reaction mixture was warmed to room temperature and stirred for 2 hours. The mixture was then re-cooled to −78° C. and triisopropyl borate (2.20 mL; 9.34 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was quenched with a few drops of saturated aqueous ammonium chloride solution, and then a few drops of saturated aqueous sodium carbonate solution were added to cleave the boronate ester. The reaction mixture was dried over magnesium sulfate to afford the boronic acid as a THF solution. To this mixture was added pinacol (3.8865 g; 32.230 mmol), and the mixture was then heated at 40° C. for 24 hours. The reaction mixture was concentrated, absorbed onto silica gel and purified by flash chromatography (40 g silica, solvent gradient: 0-50% ethyl acetate in heptane) to yield 0.2622 g (53%) of the title compound. LCMS (ESI): M+H=272.2; 1H NMR (400 MHz, DMSO) δ 8.30 (s, 1H), 2.47 (d, J=2.3 Hz, 3H), 1.32 (s, 12H).

1. temperatureThe mixture was then re-cooled to −78° C.
2. stirringThe reaction mixture was stirred at room temperature for 18 hours
3. customThe reaction mixture was quenched with a few drops of saturated aqueous ammonium chloride solution
4. additiona few drops of saturated aqueous sodium carbonate solution were added
5. dry with materialThe reaction mixture was dried over magnesium sulfate

ORD record

ord-9cb0adbfbbee42229251c2e1eb7fb43b

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623889B2