反应详情

温度

90 °C

To a suspension of Example 61A (300 mg, 0.813 mmol) and ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (342 mg, 1.219 mmol) in 10 mL dimethoxyethane/ethanol/water (7:2:3) was added sodium carbonate (345 mg, 3.25 mmol) and dichlorobis(triphenylphosphine) palladium(II) (17.09 mg, 0.024 mmol). The reaction was stirred at 90° C. for 12 hours, then cooled, and extracted with ethyl acetate. The combined organic fractions were washed with saturated sodium bicarbonate (2×), water, and brine, dried over magnesium sulfate and concentrated. The crude material was triturated with ethyl acetate, and the solid was collected by filtration. The solid was dissolved in 15 mL dioxane, treated with 6 M sodium hydroxide (1.355 ml, 8.13 mmol) and stirred at 90° C. for 12 hours. Most of the solvent was removed, and the residue was diluted with 30 mL water. The aqueous mixture was extracted with ethyl acetate (2×), and the organic fractions were discarded. The aqueous layer was made neutral (˜pH 7) with 1 M HCl. The solid was collected by filtration and dried under high-vacuum to give the title compound. 1H NMR (500 MHz, DMSO-d6) δ 12.16 (s, 1H) 8.75 (s, 1H) 7.28-7.39 (m, 2H) 7.15-7.26 (m, 1H) 6.60 (s, 1H) 6.24 (s, 1H) 3.69-3.85 (m, 3H) 2.26-2.47 (m, 4H) 1.93-2.10 (m, 1H) 1.54-1.77 (m, 1H) MS (ESI+) m/z 368.2 (M+H)+.

1. temperaturecooled
2. extractionextracted with ethyl acetate
3. washThe combined organic fractions were washed with saturated sodium bicarbonate (2×), water, and brine
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated
6. customThe crude material was triturated with ethyl acetate
7. filtrationthe solid was collected by filtration
8. dissolutionThe solid was dissolved in 15 mL dioxane
9. stirringstirred at 90° C. for 12 hours
10. customMost of the solvent was removed
11. additionthe residue was diluted with 30 mL water
12. extractionThe aqueous mixture was extracted with ethyl acetate (2×)
13. filtrationThe solid was collected by filtration
14. customdried under high-vacuum