2,3-Difluoropyridine

Pale yellow liquid

Under nitrogen protection, 2-chloro-3fluoropyridine (2.2 g, 14 mmol) was dissolved in anhydrous tetrahydrofuran (30 mL), The reaction solution was then cooled to about -78 C.Slowly add 2.5N n-butyllithium solution (6mL, 15mmol) with stirring.After the dropwise addition was completed, the reaction solution was further reacted at -78 C for 1 hour.Then, compound 1A (3 g, 11.2 mmol) dissolved in anhydrous tetrahydrofuran (20 mL) was slowly added dropwise to the reaction solution. After completion of the dropwise addition, the reaction was continued at -78 C for 2 hours.TLC monitoring showed that the reaction was over. A saturated aqueous ammonium chloride solution (250 mL) was added and extracted with ethyl acetate (3 × 100 mL).The organic phases were combined and dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the filtrate was evaporated to remove the solvent under reduced pressure.The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3/1 (V / V)), The eluent was concentrated under reduced pressure to obtain the target compound 1C (3.1 g, yield: 85%), It was a yellow oil.2, 3-Difluoropyridine (2.4 g) was dissolved in ethanol (42 ml), and hydrazine hydrate (10.5 g) was added thereto. The mixture was stirred for 3 hours under heating and refluxing. The reaction solution mentioned above was concentrated, and water was poured into the obtained residue. The mixture was subjected to extraction with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The obtained residue (2.3 g) was dissolved in ethanol (31 ml), and ethyl (ethoxymethylene)cyanoacetate (3.1 g) was added thereto. The mixture was stirred overnight under heating and refluxing. The reaction solution mentioned above was concentrated, and water was poured into the obtained residue. The mixture was subjected to extraction with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 4.1 g (yield 91%). 1H-NMR of the objective product obtained is shown below. 1H-NMR (400 MHz, CDCl3): delta 8.26 (d, 1H), 7.84 (s, 1H), 7.66 (m, 1H), 7.28 (m, 1H), 6.92 (br s, 2H), 4.31 (q, 2H), 1.37 (t, 3H).

Molecular Weight:115.08
XLogP3:1.4
Hydrogen Bond Acceptor Count:3
Exact Mass:115.02335542
Monoisotopic Mass:115.02335542
Topological Polar Surface Area:12.9
Heavy Atom Count:8
Complexity:76.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes