Dimethylformamide → 6-Bromo-3-pyridinemethanol

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%).

1. stirringstirred for a further 30 min
2. customThe reaction was quenched by addition of H2O (30 ml)
3. customThe reaction mixtures
4. extractionextracted with EtOAc (3×250 ml)
5. washThe combined organic extracts were washed with brine (100 ml)
6. customdried
7. concentrationconcentrated under reduced pressure
8. temperaturecooled to 0° C
9. temperaturethe reaction was warmed to room temperature
10. stirringstirred for 90 min
11. customwas removed under reduced pressure
12. additionthe reaction mixture was diluted with H2O (100 ml)
13. extractionAfter extraction with EtOAc (3×250 ml)
14. washthe combined organic extracts were washed with brine (50 ml)
15. customdried
16. concentrationconcentrated under reduced pressure

ORD record

ord-17c0b1fda228409984d188288562ab7d

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06900209B2