Methanol → (2-Bromo-4-chloropyridin-3-yl)methanol

Temperature

20 °C

To a solution of 2-bromo-4-chloronicotinaldehyde 160a (20 g, 90.4 mmol), N,N-dimethylacetamide (15.6 g, 180.8 mmol) and methanol (8.8 g, 271 mmol) in 1,4-dioxane (150 mL) was added sodium borohydride (1.7 g, 45.2 mmol). See FIG. 5. The mixture was stirred at 20° C. for 10 min. TLC (petroleum ether:ethyl acetate=1:1) showed that the starting material was completely consumed. The mixture was quenched with saturated aqueous ammonium chloride solution (30 mL) and water (40 mL), and extracted with EtOAc (100 mL×2). The organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with petroleum ether:ethyl acetate from 50:1 to 1:1) to afford (2-bromo-4-chloropyridin-3-yl)methanol 160b (20 g, 95%) as a white solid.

1. customwas completely consumed
2. customThe mixture was quenched with saturated aqueous ammonium chloride solution (30 mL) and water (40 mL)
3. extractionextracted with EtOAc (100 mL×2)
4. washThe organic layers were washed with brine (100 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by column chromatography on silica gel (eluting with petroleum ether:ethyl acetate from 50:1 to 1:1)

ORD record

ord-711fff05bb1f41bcb3cfbf6d1f4a3d16

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09326985B2