2-Bromopyridine → 3-Bromo-2-hydroxybenzaldehyde

Participants

Reaction Steps

A mixture of 11 (3.7 g, 8.94 mmol, 1.0 equiv), 2-bromopyridine (1.6 g, 0.95 mL, 10 mmol, 1.12 equiv), K2CO3 (3.7 g, 26.8 mmol, 3.0 equiv), dioxane (60 mL) and H2O (10 mL) was degassed with N2 for 5 min. Pd(Ph3P)4 (0.5 g, 0.43 mmol, 4.8 mole %) was added and the mixture refluxed for 8 hr, cooled to room temperature and stirred for 48 hr. The reaction suspension was diluted with EtOAc (100 mL) and the mixture filtered through Celite, washing the Celite pad with EtOAc (100 mL). The filtrate was concentrated under reduced pressure giving a yellow oil. The oil was partitioned between 1:1 EtOAc/heptanes (100 mL) and H2O (50 mL). The organic phase was washed with H2O (3×50 mL), brine (50 mL), dried over Na2SO4, filtered and the solution concentrated under reduced pressure to give a colorless oil. The crude product was absorbed onto silica gel using DCM and dry-loaded on a column of silica gel (50 g) packed in hexanes. The column was eluted with hexanes (800 mL), 3% EtOAc/hexanes (500 mL), 6% EtOAc/hexanes (500 mL), 10% EtOAc/hexanes (500 mL), and 15% EtOAc/hexanes (500 mL). Product fractions (eluted with 15% EtOAc/hexanes) were concentrated under reduced pressure yielding an oil that crystallized on pumping under high vacuum to give 1.46 g (42%) of 7 as a white solid.

Provenance & Evidence