Ethanol → 4-Pyridin-2-ylbenzaldehyde

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-formyl-phenylboronic acid (5.0 g, 33.0 mmol) and 2-bromopyridine (5.53 g, 35.0 mmol, 1.05 equiv.) in 265 mL of 4:3 toluene/95% ethanol was degassed with nitrogen for 30 minutes and then heated under a nitrogen atmosphere, resulting in a clear solution. A slurry of Pd(PPh3)4 (0.77 g) in 50 mL of a 4:4 mixture of toluene and 95% ethanol was added, followed by 50 mL of 3M aqueous Na2CO3. The resulting mixture was gently refluxed at 77° C. After 16 hours, the reaction mixture was cooled to room temperature, and the solid removed by filtration. The filtrate was transferred to a separatory funnel, and the layers separated. The aqueous layer was extracted with toluene (3×50 mL). The combined organics were washed with water, then saturated sodium chloride, and dried over sodium sulfate. The solution was filtered, and the filtrate concentrated under reduced pressure to give a yellow oil. Purification by Biotage chromatography (40+M cartridge; gradient, 0 to 5% methanol/dichloromethane) gave 4.13 g (68%) of (3) as a light-yellow solid. TLC Rf(hexane/ethyl acetate, 2:1)=0.25; 1H NMR (CDCl3) δ 10.1 (s, HCO), 8.77 (d, 1H), 8.20 (d, 2H), 8.00 (d, 2H), 7.81 (m, 2H), 7.31 (q, 1H); MS (M)+=184; HPLC tR 1.2 minutes.

Provenance & Evidence