2,3-Dichloropyridine → 4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-1,4-benzoxazine

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Reaction Steps

To a solution of 3,4-dihydro-2H-1,4-benzoxazine (198 mg, 1-47 mmol) in dry dioxane (3 mL) was added 60% sodium hydride/mineral oil (90 mg, 2.25 mmol) and let stir at ambient temperature for 15 min. Then 2,3-dichloropyridine (264 mg, 1.78 mmol) was added and the mixture was warm to 80 C. Over 24 hours periodically added small portions (˜10 mg) of NaH and another 90 mg of 2,3-dichloropyridine until all of the benzoxazine was gone. Cooled and diluted with ethyl acetate, neutralized with acetic acid and then washed with NaHCO3 solution, followed with water. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent evaporated. This residue was purified by chromatography on silica gel eluting with a 10-15% acetone/hexane gradient to give the title compound as a viscous oil which slowly solidified (168 mg, 46% yield). 1H-NMR (500 MHz, CDCl3): δ 8.35 (1H, d, J=4.6 Hz), 7.74 (1H, d, J=8.1 Hz), 7.05 (1H, dd, J=4.7, 8.0 Hz), 6.90 (1H, d, J=7.4 Hz), 6.83 (1H, t, J=7.3 Hz), 6.75 (1H, t, J=7.3 Hz), 6.55 (1H, d, J=7.8 Hz), 4.39 (2H, t, J=4.3), 3.84 (2H, t, J=4.Hz). m/e (m+1): 247.0

Provenance & Evidence