Potassium Phosphate, Tribasic → HCID 58042484, compound

Participants

Reaction Conditions

Reaction Steps

2-bromo-3-trifluoromethylpyridine (5 g, 22.1 mmol), cyclopropyl boronic acid (2.09 g, 24.3 mmol), and tribasic potassium phosphate (14.1 g, 66.4 mmol) were suspended in a mixture of toluene (150 mL) and water (30 mL), with rapid stirring. The suspension was heated to 80° C., and the solvent de-gassed by direct bubbling of N2 gas through the suspension for 30 minutes. The reaction was then heated to 95° C., and tricyclohexyl phosphine (620 mg, 2.21 mmol) followed by palladium acetate (248 mg, 1.12 mmol) were added. The reaction was left to stir and heat at 95° C. for 6 hours. The reaction was cooled to room temperature, and filtered through a plug of Arbocel™, eluting with ethyl acetate. The solvent was removed to leave a dark yellow oil. TBME was added (300 mL), and the organic phase washed with 2M HCl solution (3×200 mL). The organics were discarded. TBME (300 mL) was added to the combined aqueous layers, and solid sodium bicarbonate was added until the aqueous layer reached pH 7. The organic layer was removed, and the aqueous layer was extracted with TBME (2×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 4:1 heptane:ethyl acetate, affording the title compound as a colourless oil (400 mg, 10%).

Provenance & Evidence