反应详情

温度

85 °C

A mixture of (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid (2.22 g, 10 mmol), 3-bromobenzonitrile (2.18 g, 12 mmol), tetrakis(triphenylphosphine)palladium (0) (0.6 g, 0.52 mmol), and sodium carbonate (2.2 g, 21 mmol) in a mixture of DME and water (70 mL/15 mL) was degassed to remove the oxygen and then heated at 85° C. under a blanket of nitrogen for 3 hours. The reaction mixture was cooled to ambient temperature and quenched with a saturated aqueous ammonium chloride solution (20 mL). Ethyl acetate (100 mL) was added and organic layer was separated. The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by a silica gel flash chromatography (hexane ethyl acetate/1:1) to give 3-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-benzonitrile as an off-white solid (0.7 g, 25%): mp 236-237° C.; 1H-NMR (DMSO-d6) δ 10.34 (s, 1H, D2O exchangeable), 8.21 (s, 1H), 8.02 (d, 1H, J=8.1 Hz), 7.79 (d, 1H, J=7.7 Hz), 7.60-7.70 (m, 3H), 6.98 (d, 1H, J=8.2 Hz), 1.71 (s, 6H), Anal. Calc. For C17H14N2H2O: C, 72.89; H, 5.11; N, 10.00. Found: C, 72.75; H, 5.05; N, 9.65.

1. customwas degassed
2. customto remove the oxygen
3. temperatureThe reaction mixture was cooled to ambient temperature
4. customquenched with a saturated aqueous ammonium chloride solution (20 mL)
5. additionEthyl acetate (100 mL) was added
6. customorganic layer was separated
7. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
8. washThe combined organic layers were washed with brine
9. dry with materialdried with MgSO4
10. customThe solvent was removed in vacuo
11. customthe residue was purified by a silica gel flash chromatography (hexane ethyl acetate/1:1)