反应详情

温度

75 °C

To a flask containing (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl trifluoromethanesulfonate (1.22 g, 2.187 mmol) was added phosphoric acid, potassium salt (1.393 g, 6.56 mmol), ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (0.613 g, 2.187 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-phos) (0.067 g, 0.164 mmol), and palladium(II)acetate (0.025 g, 0.109 mmol). The mixture was diluted with 1,4-dioxane (10 mL) and water (1 mL), was flushed with nitrogen, then was sealed and heated to 75° C. After 15 h of heating, the mixture was cooled to rt and was concentrated under reduced pressure. The residue was diluted with water (40 mL) and was extracted with ethyl acetate (3×50 mL). The organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography using a 10-70% EtOAc in hexanes gradient and an 80 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate (806 mg, 1.434 mmol, 65.6% yield) as an off-white solid. LCMS: m/e 562.7 (M+H)+, 2.17 min (method 1).

1. customwas flushed with nitrogen
2. customwas sealed
3. temperatureAfter 15 h of heating
4. temperaturethe mixture was cooled to rt
5. concentrationwas concentrated under reduced pressure
6. additionThe residue was diluted with water (40 mL)
7. extractionwas extracted with ethyl acetate (3×50 mL)
8. washThe organic layers were washed with brine
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by flash chromatography
13. additionThe fractions containing the expected product
14. concentrationconcentrated under reduced pressure