Water → 5-Bromo-3-fluoropyridine-2-carbaldehyde

Temperature

-78 °C

To a solution of crude 5-bromo-3-fluoro-N-methoxy-N-methylpyridine-2-carboxamide (27.94 g, 106.2 mmol) in THF (350 mL) at −78° C. was added lithium aluminum hydride (1M in THF, 45.67 mL, 45.67 mmol) dropwise. The reaction was stirred at −78° C. for 2 hours, then H2O (100 mL) and brine (100 mL) were added. The mixture was warmed to RT and partially concentrated in vacuo, diluted with ethyl acetate and filtered through celite. The aqueous layer was extracted 4× with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was filtered through a silica gel plug with 10% ethyl acetate in hexanes to provide 5-bromo-3-fluoropyridine-2-carbaldehyde that gave proton NMR spectra consistent with theory.

1. temperatureThe mixture was warmed to RT
2. concentrationpartially concentrated in vacuo
3. additiondiluted with ethyl acetate
4. filtrationfiltered through celite
5. extractionThe aqueous layer was extracted 4× with ethyl acetate
6. washThe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. filtrationThe residue was filtered through a silica gel plug with 10% ethyl acetate in hexanes

ORD record

ord-46db81f51f8f4d2189a77f01877d23ca

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07163951B2