反应详情

温度

85 °C

A mixture of 4-bromo-2-methoxy-1-nitrobenzene, (I24) (2.364 g, 10.2 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (3.00 g, 9.70 mmol), potassium carbonate (4.02 g, 29.1 mmol) and DMF (60 mL) was degassed with three vacuum/nitrogen cycles then PdCl2(dppf)-DCM solvate (450 mg, 6 mol %) added under nitrogen in a Schlenk tube. A second tube was prepared in the same manner (i.e. a total of 6.00 g starting boronate), and both tubes were heated to 85° C. under nitrogen. After 17 hours both tubes were cooled under nitrogen and added to 5% w/v aqueous lithium chloride (600 mL). The resulting mixture was extracted with ether (300 mL) and ethyl acetate (3×300 mL). The combined organic extracts were washed with water (600 mL) and brine (600 mL), dried (sodium sulphate) then evaporated to dryness. The residue was chromatographed (120 g silica cartridge, 0-60% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I25) (5.863 g, 91% yield) as a yellow solid; 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J=8.5 Hz, 1H), 7.04-6.97 (m, 2H), 6.17 (s, 1H), 4.12 (d, J=2.5 Hz, 2H), 3.98 (s, 3H), 3.65 (t, J=5.6 Hz, 2H), 2.52 (s, 2H), 1.49 (s, 9H). LCMS Method C: rt 6.27 min; m/z 279.0 [M-tBu+2H]+, 235.1 [M-Boc+2H]+.

1. customwas degassed with three vacuum/nitrogen cycles
2. additionPdCl2(dppf)-DCM solvate (450 mg, 6 mol %) added under nitrogen in a Schlenk tube
3. customA second tube was prepared in the same manner (i.e. a total of 6.00 g starting boronate), and both tubes
4. temperatureAfter 17 hours both tubes were cooled under nitrogen
5. additionadded to 5%
6. extractionThe resulting mixture was extracted with ether (300 mL) and ethyl acetate (3×300 mL)
7. washThe combined organic extracts were washed with water (600 mL) and brine (600 mL)
8. dry with materialdried (sodium sulphate)
9. customthen evaporated to dryness
10. customThe residue was chromatographed (120 g silica cartridge, 0-60% ethyl acetate/petroleum benzine 40-60° C.)