Dimethylformamide → 3-Fluoro-2-pyridinecarboxaldehyde

Temperature

-17.5 °C

To a solution of DABCO (8.8 g, 78.2 mmol) in anhydrous diethyl ether (250 mL) at −25° C. was added n-BuLi (1.6 M in hexanes, 49 mL, 78.2 mmol). The mixture was stirred between −25 to −10° C. for 45 min and then cooled to −70° C. To the above solution was added 3-fluoropyridine (5.9 mL, 71 mmol) dropwise. The reaction was stirred between −70 to −60° C. for 1.5 h before DMF (11.0 mL, 2.0 eq.) was added. After 1.0 h stirring at −70° C., water (150 mL) was added and warmed up to rt. The layers were separated and the aqueous layer was extracted with methylene chloride (5×100 mL). The combined organic layer was washed with brine and dried over Na2SO4. After removal of solvent, the crude was purified by silica gel column chromatography using gradient EtOAc in hexanes to give 5.4 g (55-60% yield) of 65A. 1H NMR (400 MHz, CDCl3) δ ppm 7.54-7.57 (m, 2H) 8.61 (d, J=2.20 Hz, 1H) 10.20 (s, 1H).

1. temperaturecooled to −70° C
2. additionwas added
3. stirringAfter 1.0 h stirring at −70° C.
4. temperaturewarmed up to rt
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with methylene chloride (5×100 mL)
7. washThe combined organic layer was washed with brine
8. dry with materialdried over Na2SO4
9. customAfter removal of solvent
10. customthe crude was purified by silica gel column chromatography

ORD record

ord-b1d244bd14db4177a8f54d4f063388c4

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222453B2