Dimethylformamide → 6-Bromo-3-pyridinemethanol

Participants

Reaction Steps

Two simultaneous reactions were conducted whereby: BuLi (29.9 ml of a 1.6 M solution in hexanes, 47.7 mmol) was added to a stirred solution of 2,5-dibromopyridine (10.3 g, 43.4 mmol) in Et2O (250 ml) at −78° C. under nitrogen over 10 min. The resulting mixture was stirred for 15 min, then DMF (10.07 ml, 0.13 mol) was added. The reaction was allowed to warm to room temperature and then stirred for a further 30 min. The reaction was quenched by addition of H2O (30 ml). The reaction mixtures were combined and extracted with EtOAc (3×250 ml). The combined organic extracts were washed with brine (100 ml), dried and concentrated under reduced pressure. The crude residue was taken up in EtOH (100 ml) and cooled to 0° C. NaBH4 (3.26 g, 86.4 mmol) was added portionwise over 10 min, the reaction was warmed to room temperature and stirred for 90 min. NH4Cl (sat., 50 ml) was added cautiously, most of the EtOH was removed under reduced pressure and the reaction mixture was diluted with H2O (100 ml). After extraction with EtOAc (3×250 ml), the combined organic extracts were washed with brine (50 ml), dried and concentrated under reduced pressure. Column chromatography on silica using 75-80% Et2O/hexanes as eluent gave the title alcohol (5.65 g, 35%).

Provenance & Evidence