反应详情

温度

110 °C

A mixture of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (45 mg, 0.14 mmol), 4-[3-(4-bromophenoxy)-propyl]-morpholine (42 mg, 0.14 mmol) prepared using the procedure in Le Sann, C.; Huddleston, J.; Mann, J. Tetrahedron, 2007, 63, 12903-12911, and 2M potassium carbonate solution (0.28 mL, 0.56 mmol) in toluene (0.9 mL) and ethanol (0.3 mL) was degassed with nitrogen for 5 minutes then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (6.0 mg, 0.007 mmol). The reaction vessel was sealed and heated at 110° C. for 2.5 h. The cooled reaction mixture was poured into water and ethyl acetate. The layers were separated and the aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified using flash column chromatography eluting with heptanes/ethyl acetate (4:1 to 0:1) and ethyl acetate/methanol (9:1) to give the title compound (24 mg, 40%). MS (ES+) 429.2 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.37 (br. s., 1H), 7.98 (s, 1H), 7.95 (s, 1H), 7.55 (s, 1H), 7.33 (d, J=8.59 Hz, 2H), 6.97 (d, J=8.78 Hz, 2H), 4.11 (t, J=5.95 Hz, 2H), 3.84 (s, 3H), 3.79 (t, J=4.69 Hz, 4H), 2.89-2.97 (m, 2H), 2.86 (m, 4H), 2.11 (dt, J=15.42, 5.86 Hz, 2H).

1. customprepared
2. customThe reaction vessel was sealed
3. customThe cooled reaction mixture
4. customThe layers were separated
5. extractionthe aqueous layer was back-extracted twice with ethyl acetate
6. dry with materialThe combined organic layers were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified
10. washeluting with heptanes/ethyl acetate (4:1 to 0:1) and ethyl acetate/methanol (9:1)