Dimethylformamide → 3-Fluoro-2-pyridinecarboxaldehyde

Temperature

-70 °C

To a stirred solution of DABCO (262.4 g, 2342 mmol) in anhydrous Et2O (2.1 L) at −25° C. in a 10 L 3-neck round bottom flask was added n-BuLi (2.5 M in hexane, 938 mL, 2342 mmol). The mixture was stirred between −25° C. to −10° C. for 45 min. and then cooled to −70° C. To the above solution was added 3-fluoropyridine (206.7 g, 2129 mmol) dropwise, and the reaction was stirred between −70° C. to −60° C. for 1.5 h before DMF (344 mL, 4258 mmol) was added. The progress of the reaction was monitored by TLC (5% EtOAc in Petroleum ether). After 1 h stirring at −70° C., water (800 mL) was added, and the reaction was allowed to warm to rt. The layers were separated, and the aqueous layer was extracted with DCM (5×1 L). The combined organic layers were washed with brine and dried over sodium sulfate. After removal of solvent the initially obtained product was purified by silica gel chromatography using a gradient of EtOAc in hexane to give the title compound as pale yellow oil. 1H-NMR (400 MHz, CDCl3): δ ppm 10.21 (s, 1H), 8.63 (t, J=2.2 Hz, 1H), 7.54-7.57 (m, 2H). MS (ESI pos. ion) m/z: 126.0 (M+H).

1. additionwas added
2. stirringAfter 1 h stirring at −70° C.
3. temperatureto warm to rt
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with DCM (5×1 L)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over sodium sulfate
8. customAfter removal of solvent the initially obtained product
9. customwas purified by silica gel chromatography

ORD record

ord-e48e8f4f7d15481790ace23bb6ba7b4a

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08710043B2