Lithium Chloride → Ethyl 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(benzoyloxymethyl)-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)isoxazole-3-carboxylate

温度

85 °C

To a sealable vial containing ethyl 5-(tributylstannyl)isoxazole-3-carboxylate (0.052 g, 0.122 mmol) was added ((1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-3a-yl)methyl benzoate (0.075 g, 0.111 mmol), lithium chloride (0.014 g, 0.332 mmol), and tetrakis(triphenylphosphine)palladium(0) (6.40 mg, 5.54 μmol). The mixture was diluted with 1,4-Dioxane (2 mL) and was flushed with N2. The vial was sealed and heated to 85° C. After 15.5 h of heating, the mixture was cooled to rt, was diluted with water (4 mL), and was extracted with dichloromethane (3×4 mL). The combined organic layers were dried over Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by Biotage flash chromatography using a 0-10% EtOAc in hexanes gradient. The fractions containing the expected product were combined and concentrated under reduced pressure. Ethyl 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(benzoyloxymethyl)-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)isoxazole-3-carboxylate was isolated as an off-white foam (0.015 g total mass, 0.022 mmol, 20.3% yield). LCMS: m/e 668.53 (M+H)+, 3.11 min (method 1).

1. customwas flushed with N2
2. customThe vial was sealed
3. temperatureAfter 15.5 h of heating
4. temperaturethe mixture was cooled to rt
5. additionwas diluted with water (4 mL)
6. extractionwas extracted with dichloromethane (3×4 mL)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. customThe drying agent was removed by filtration
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe residue was purified by Biotage flash chromatography
11. additionThe fractions containing the expected product
12. concentrationconcentrated under reduced pressure

ORDレコード

ord-ca74c13023ec4048a979d625329b9c0d

出典データセット

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08754068B2