Sodium Carbonate → 4-(5-Ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carbonitrile

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Reaction Steps

(5-Ethoxy-2-fluoro-phenyl)boronic acid (1.71 g, 9.3 mmol) was added to a solution of 4-bromo-5,6-dimethyl-pyridine-2-carbonitrile (which may be prepared as described in Description 144) (1.96 g, 9.3 mmol) in monoglyme (50 mL). To this was added a hot solution of sodium carbonate (2.96 g, 27.9 mmol) in water (15 mL) under N2 at ambient temp. Bis(triphenylphosphine)palladium (II) dichloride (326.38 mg, 0.4700 mmol) was then added and the whole stirred mixture was degassed by bubbling N2 through it for 10 mins. The vigorously stirred mixture was then heated at reflux for 2 h. The solution was cooled and diluted with DCM (100 ml) and washed with water (75 ml), dried (Na2SO4) and evaporated to a black solid. This was dissolved in DCM (15 ml) and the solution applied to a 100 g SiO2 chromatography cartridge which was then eluted on a Biotage SP4 system with a gradient of EtOAc-isohexane (0-30%). Relevant fractions were pooled and evaporated to a colourless solid which was dried at RT for 3 h under vacuum to give 4-(5-ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carbonitrile (D51) (1.87 g):

Provenance & Evidence