2-CHLORO-6-FLUOROQUINOLINE

General procedure: To a stirred solution of the appropriate azine N-oxides in anhydrous CH[0449] 6-fluoro-1, 2-dihydroquinolin-2-one (7.8 g, 47.8 mmol) was suspended in phosphorus oxychloride (72.2 g, 470.9 mmol) and stirred for 4 hours at 100° C. in an oil bath. The reaction mixture was concentrated under vacuum to remove the excess phosphorus oxychloride and then ice-water (200 ml) was added. The precipitate that formed was washed with water (2×80 ml) and dried to give 2-chloro-6-fluoroquinoline as a off-white solid (6.8 g, 78percent); (ES, m/z): [M+H][0449] 6-fluoro-1, 2-dihydroquinolin-2-one (7.8 g, 47.8 mmol) was suspended in phosphorus oxychloride (72.2 g, 470.9 mmol) and stirred for 4 hours at 100 C. in an oil bath. The reaction mixture was concentrated under vacuum to remove the excess phosphorus oxychloride and then ice-water (200 ml) was added. The precipitate that formed was washed with water (2×80 ml) and dried to give 2-chloro-6-fluoroquinoline as a off-white solid (6.8 g, 78%); (ES, m/z): [M+H]+ 182; 1H NMR (300 MHz, DMSO): delta 8.43 (d, J=8.4 Hz, 1H), 8.01 (dd, J=5.4 Hz, 9.3 Hz, 1H), 7.87 (dd, J=3.0 Hz, 9.3 Hz, 1H), 7.72-7.78 (m, 1H), 7.45 (d, J=8.4 Hz, 1H).A solution of A solution of Pd(PPh3)4 (54 mg, 0.05 mmol, 0.10 equiv) was added over a solution of 2-chloro-6- fiuoroquinoline (84 mg, 0.46 mmol, 1.00 equiv)and 2-methyl-3-nitro-6- (tributylstannyl)pyridine (200 g, 468.20 mmol, 1.00 equiv) in toluene (2 mL). The resulting mixture was stirred for 12 h at 110 C. The reaction was cooled down to room temperature, quenched with water and extracted with ethyl acetate three times. The combined organic layers were dried with MgS04 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1 :2) to afford the desired final product as a colorless oil in 91% yield.Pd(PPh3)4 (54 mg, 0.05 mmol, 0.10 equiv) was added over a solution of 2-chloro-6- fluoroquinoline (84 mg, 0.46 mmol, 1.00 equiv)and 2-methyl-3-nitro-6-(tributylstannyl)pyridine (200 g, 468.20 mmol, 1.00 equiv) in toluene (2 mL). The resulting mixture was stirred for 12 h at 110 C. The reaction was cooled down to room temperature, quenched with water and extracted with ethyl acetate three times. The combined organic layers were dried with MgSCri and concentrated under reduced pressure. The resulting residue was purified by silica gel (1072) chromatography with ethyl acetate/petroleum ether (1 :2) to afford the desired final product as a colorless oil in 91% yield.

Molecular Weight:181.59
XLogP3:2.8
Hydrogen Bond Acceptor Count:2
Exact Mass:181.0094550
Monoisotopic Mass:181.0094550
Topological Polar Surface Area:12.9
Heavy Atom Count:12
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes