反应详情

温度

75 °C

To a vial 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 (0.65 g, 1.165 mmol) was added phosphoric acid, potassium salt (0.742 g, 3.50 mmol), (R)-benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (0.8 g, 2.338 mmol) (enantiomer 1 prepared above), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-phos) (0.072 g, 0.175 mmol) and palladium(II) acetate (0.026 g, 0.117 mmol). The mixture was diluted with 1,4-dioxane (10 mL) and water (1 mL), flushed with nitrogen, then the vial was sealed and heated to 75° C. After 6 h of heating, the mixture was cooled to rt, diluted with water (20 mL) and brine (20 mL), and was extracted with dichloromethane (5×40 mL). The organic layers were dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography using a 10-60% ethyl acetate in hexanes gradient and a 40 g silica gel column. The fractions containing the expected product were combined and were concentrated under reduced pressure to give (R)-benzyl 4-((1R,3 aS,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 (0.488 g, 0.782 mmol, 67.1% yield) as an off-white solid. LCMS: m/e 624.65 (M+H)+, 2.18 min (method 1). 1H NMR (500 MHz, chloroform-d) δ=7.40-7.30 (m, 5H), 5.35 (br. s., 1H), 5.18 (dd, J=6.2, 1.8 Hz, 1H), 5.14 (s, 2H), 4.73 (d, J=2.0 Hz, 1H), 4.60 (s, 1H), 2.65-2.50 (m, 2H), 2.38-2.30 (m, 2H), 2.25-1.94 (m, 5H), 1.70 (s, 3H), 1.07 (s, 3H), 0.96 (s, 3H), 0.94 (s, 3H), 0.92 (s, 3H), 0.86 (s, 3H), 1.80-0.83 (m, 23H).

1. customflushed with nitrogen
2. customthe vial was sealed
3. temperatureAfter 6 h of heating
4. temperaturethe mixture was cooled to rt
5. additiondiluted with water (20 mL) and brine (20 mL)
6. extractionwas extracted with dichloromethane (5×40 mL)
7. dry with materialThe organic layers were dried with sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by flash chromatography
11. additionThe fractions containing the expected product
12. concentrationwere concentrated under reduced pressure