Dimethylformamide → (6-Bromopyridin-2-yl)methanol

Temperature

-78 °C

n-BuLi (2.5M, 20.0 mL, 50.0 mmol) in tetrahydrofuran (40 mL) was cooled to −78° C. 2,6-Dibromopyridine (11.85 g, 50.0 mmol) in 70 mL tetrahydrofuran was added dropwise while keeping the internal temperature of the reaction below −70° C. The resulting dark green solution stirred for 15 min at this temperature upon which N,N-dimethylformamide (6.0 mL, 78 mmol) was added over a period of 30 seconds. The reaction stirred at −78° C. for 15 min and methanol (50 mL) and acetic acid (3.2 mL) were added. Sodium borohydride (1.89 g, 50.0 mmol) was added last. The reaction was allowed to warm to room temperature. The solution was carefully quenched with sat. ammonium chloride and then extracted with ethyl acetate (2 times). The organic layers were combined and washed with brine, dried over sodium sulfate, filtered, and concentrated. Flash chromatography (25% ethyl acetate/hexanes) gave 2.57 g (27% yield) of the alcohol as a pale yellow oil.

1. customthe internal temperature of the reaction below −70° C
2. additionwas added over a period of 30 seconds
3. temperatureto warm to room temperature
4. customThe solution was carefully quenched with sat. ammonium chloride
5. extractionextracted with ethyl acetate (2 times)
6. washwashed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-7717048464f9402cb9afbfbeab620e08

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897607B2