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

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)+.

1. customprepared
2. customin Synthesis, 2001
3. stirringthe reaction mixture was stirred for 15 minutes at −78° C. under Ar-atm
4. stirringthe reaction mixture was stirred for 2 h −78° C. under Ar-atm
5. customThe reaction mixture was quenched
6. additionby adding HOAc (3 mL) and TFA (3 mL)
7. concentrationconcentrated
8. customthe residue was purified by flash column on silica gel eluting with hexane/EtOAc/MeOH//750:250:50

ORD record

ord-23afa69a106145ea946cd42c53924a03

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07732613B2