Methyl 3-bromoisonicotinate → (3-Bromopyridin-4-yl)methanol

Temperature

-15 °C

Diisobutylaluminum hydride (1.0M solution in tetrahydrofuran, 14 mL) was added to a solution of methyl 3-bromoisonicotinate (1.0 g, 4.6 mmol) in methylene chloride (15 mL) cooled at −15° C. After 1 hour at this temperature, the reaction was quenched by dropwise addition of saturated aqueous ammonium chloride solution (3 mL). The reaction mixture was diluted with ethyl acetate (50 mL) and washed with 1.0M citric acid solution in water (20 mL). The organic layer was separated, and the aqueous layer was neutralized via addition of solid sodium bicarbonate solution and then extracted with ethyl acetate (50 mL). The combined organic portions were dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-75% ethyl acetate in heptane) to afford the title compound as a white solid (110 mg, 75%), which was used in the next step without further purification.

1. customthe reaction was quenched by dropwise addition of saturated aqueous ammonium chloride solution (3 mL)
2. additionThe reaction mixture was diluted with ethyl acetate (50 mL)
3. washwashed with 1.0M citric acid solution in water (20 mL)
4. customThe organic layer was separated
5. additionthe aqueous layer was neutralized via addition of solid sodium bicarbonate solution
6. extractionextracted with ethyl acetate (50 mL)
7. dry with materialThe combined organic portions were dried over sodium sulfate
8. filtrationfiltered
9. customevaporated in vacuo
10. customto afford a residue that
11. customwas purified by flash chromatography (silica, 4 g, ISCO, 0-75% ethyl acetate in heptane)

ORD record

ord-2f9c8fe9d32848069f8bde8f5c24076e

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206175B2