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 mixture was stirred between −70° C. to −60° C. for 1.5 h before DMF (344 mL, 4258 mmol) was added. The progress of 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 sulphate. After removal of solvent, the residue was purified by silica gel chromatography using a gradient of EtOAc in hexane to give 3-fluoropicolinaldehyde as a 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. customThe progress of reaction
3. stirringAfter 1 h stirring at −70° C.
4. temperatureto warm to rt
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with DCM (5×1 L)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over sodium sulphate
9. customAfter removal of solvent
10. customthe residue was purified by silica gel chromatography

ORD record

ord-05e3ad18d50943b5a489366637e3494d

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778941B2