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

To a solution of 2-bromo-5-fluoropyridine (3.67 g, 20.8 mmol) in toluene (100 mL) was added dropwise n-butyl lithium (15.6 mL, 1.6 M hexane solution, 25.0 mmol) under nitrogen atmosphere at −78° C., which was stirred for 30 minutes. N,N-Dimethylformamide (8.05 mL, 104.0 mmol) was added dropwise to this solution at −78° C., and stirred for 20 minutes at 0° C. This reaction solution was vigorously stirred after addition of water and tetrahydrofuran. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. Sodium borohydride (1.58 g, 41.8 mmol) was added to the filtrate at 0° C., and stirred for 1 hour at room temperature. This reaction solution was partitioned by addition of 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. The resulting residue was purified by NH silica gel column chromatography (hexane:diethyl ether=1:2) to obtain the title compound (945 mg, 36%).

1. stirringstirred for 20 minutes at 0° C
2. stirringThis reaction solution was vigorously stirred
3. customThe organic layer was separated
4. washwashed with water and saturated aqueous sodium chloride
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. stirringstirred for 1 hour at room temperature
8. customThis reaction solution was partitioned by addition of water and tetrahydrofuran
9. customThe organic layer was separated
10. washwashed with saturated aqueous sodium chloride
11. dry with materialdried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationThe filtrate was concentrated under a reduced pressure
14. customThe resulting residue was purified by NH silica gel column chromatography (hexane:diethyl ether=1:2)

ORD record

ord-e4640e3b3ac64258957448a8f9232dc4

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507530B2