Reacción #556114

Ecuación de reacción

triisopropyl borate

2-chloro-3-fluoro-5-iodo-4-methyl-pyridine

tetrahydrofuran

THF

→

boronic acid

2-chloro-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe mixture was then re-cooled to −78° C.
2. 2
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 18 hours
3. 3
   OtroThe reaction mixture was quenched with a few drops of saturated aqueous ammonium chloride solution
4. 4
   workup.ADDITIONa few drops of saturated aqueous sodium carbonate solution were added
5. 5
   SecadoThe reaction mixture was dried over magnesium sulfate

Procedimiento

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).

Fuente