Dimethylformamide → (5-Chloropyridin-2-yl)methanol

To a mixture of 2-bromo-5-chloropyridine (2.0 g, 10.4 mmol) and toluene (50 ml) was added a 1.6 M n-butyl lithium hexane solution (7.8 mL, 12.5 mmol) at −78° C., which was stirred for 1 hour. N,N-dimethylformamide (4.0 mL, 52.0 mmol) was then added dropwise into the mixture at the same temperature, which was then stirred for a further 15 minutes at room temperature. Water and tetrahydrofuran were added to this reaction solution, followed by vigorous stirring. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. Sodium borohydride (1.18 g, 31.2 mmol) was added at 0° C. to the filtrate, and stirred for 1 hour at room temperature. This reaction solution was partitioned into water and tetrahydrofuran. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (hexane:diethyl ether=1:2) to obtain the title compound (706 mg, 47%).

1. stirringwas then stirred for a further 15 minutes at room temperature
2. customThe organic layer was separated
3. washwashed with water and saturated aqueous sodium chloride
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. stirringstirred for 1 hour at room temperature
7. customThis reaction solution was partitioned into water and tetrahydrofuran
8. customThe organic layer was separated
9. washwashed with saturated aqueous sodium chloride
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationfiltered
12. concentrationThe filtrate was concentrated under a reduced pressure
13. customthe resulting residue was purified by NH silica gel column chromatography (hexane:diethyl ether=1:2)

ORD record

ord-913503cedd274e66b170f2cb78b57930

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07691882B2