Sodium hydride → 2-(2-Bromopyridin-3-yl)acetaldehyde

To a white suspension of sodium hydride (1.36 g, 34 mmol) in DMSO (16 mL) at room temperature was added clear solution of (methoxymethyl)triphenyl)phosphonium chloride in DMSO (40 mL). The mixture became a yellow suspension. To the above suspension was added 2-bromonicotinaldehyde (2.48 g, 13.3 mmol) in DMSO (16 mL) dropwise. The mixture was stirred at room temperature for 20 hours then treated with excess sodium bicarbonate (sat), extracted with ether. The combined ether layer was washed with brine, dried over magnesium sulfate and concentrated. Purification by chromatography on silica gel gave E and Z mixture of 2-bromo-3-(2-methoxyvinyl)pyridine (1.88 g, 66%) as yellow oil. A solution of E and Z mixture of 2-bromo-3-(2-methoxyvinyl)pyridine(1.88 g, 8.79 mmol) in formic acid (96%, 10 mL) was stirred at 60° C. for 16 hours and at 80° C. for 3 hours before cooled to room temperature. Most of formic acid was removed. The mixture was diluted with ethyl acetate, washed with sodium bicarbonate and brine, dried over magnesium sulfate and concentrated. Purification by chromatography on silica gel gave 2-(2-bromopyridin-3-yl)acetaldehyde (864 mg, 53% yield) as yellow solid.

1. extractionextracted with ether
2. washThe combined ether layer was washed with brine
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated
5. customPurification by chromatography on silica gel
6. customgave
7. stirringwas stirred at 60° C. for 16 hours and at 80° C. for 3 hours
8. temperaturebefore cooled to room temperature
9. customMost of formic acid was removed
10. additionThe mixture was diluted with ethyl acetate
11. washwashed with sodium bicarbonate and brine
12. dry with materialdried over magnesium sulfate
13. concentrationconcentrated
14. customPurification by chromatography on silica gel

ORD-Eintrag

ord-5f37759896004545a1bf8b5cf50f2370

Quelldatensatz

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08735399B2