Benzaldehyde → 3-Bromo-5-(hydroxy(phenyl)methyl)pyridin-4-ol

Participants

Reaction Steps

To a heterogeneous mixture of 3,5-dibromo-4-hydroxypyridine (2.53 g, 10 mmol, prepared following the procedure in Synthesis, 2001, No. 14, 2175-2179) in anhydrous THF (20 mL) at −78° C. under Ar-atm was added phenylmagnesium bromide solution (11 mL of 1 M solution in THF, 11 mmol). After stirring for 15 min. was added nBuLi solution (5.5 mL of 2 M solution in cyclohexane), and the reaction mixture was stirred for 15 minutes at −78° C. under Ar-atm. To this mixture benzaldehyde (2.15 mL, 21 mmol) was added and the reaction mixture was stirred for 2 h −78° C. under Ar-atm. The reaction mixture was quenched by adding HOAc (3 mL) and TFA (3 mL), concentrated and the residue was purified by flash column on silica gel eluting with hexane/EtOAc/MeOH//750:250:50 followed by hexane/EtOAc/MeOH/Et3N//460:460:50:10 to obtain the desired product (2.85 g, 91%) as a white solid. 1H NMR (CD3OD) δ 8.13 (s, 1H), 8.04 (s, 1H), 7.41-7.20 (m, 5H), 5.94 (s, 1H); MS(ESI+) m/z 280, 282 (M+H)+.

Provenance & Evidence