Sodium Hydroxide → (4-Chloropyridin-2-yl)methanol

To a mixture of 4-chloro-2-picoline (1.0 g, 7.84 mmol) and dichloromethane (20 mL), was added m-chloroperbenzoic acid (3.5 g, 13.2 mmol) on an ice bath, which was stirred for 1.5 hours at room temperature. Water and sodium hydrogencarbonate were added to the reaction, followed by extraction with dichloromethane. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. Acetic anhydride (20 mL) was added to the residue obtained by concentrating the filtrate under a reduced pressure, and this was stirred for 1 hour at 100° C. The reaction mixture was cooled to room temperature and concentrated under a reduced pressure. A 5 N aqueous sodium hydroxide solution (1.57 mL, 7.87 mmol) was added to a mixture of the resulting residue and methanol (20 mL) on an ice bath, which was stirred for 1.5 hours at room temperature. Water was added to the mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=6:1) to obtain the title compound (200 mg, 18%).

1. extractionfollowed by extraction with dichloromethane
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. additionAcetic anhydride (20 mL) was added to the residue
7. customobtained
8. concentrationby concentrating the filtrate under a reduced pressure
9. stirringthis was stirred for 1 hour at 100° C
10. temperatureThe reaction mixture was cooled to room temperature
11. concentrationconcentrated under a reduced pressure
12. stirringwhich was stirred for 1.5 hours at room temperature
13. extractionwas then extracted with ethyl acetate
14. customThe organic layer was separated
15. washwashed with water and saturated aqueous sodium chloride
16. dry with materialdried over anhydrous magnesium sulfate
17. filtrationfiltered
18. concentrationThe filtrate was concentrated under a reduced pressure
19. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=6:1)

ORD record

ord-e07a61418e704de8998cfd1aaf0daf6b

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841327B2