反应详情

温度

75 °C

To a solution of (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(6,6-bis(isopropoxycarbonyl)spiro[3.3]hept-1-en-2-yl)-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]chrysene-3a-carboxylic acid (0.025 g, 0.021 mmol (based on 60% purity)) in 1,4-dioxane (2 mL) was added NaOH (1N) (0.25 ml, 0.250 mmol). The mixture was heated to 75° C. for 66 h, then was cooled to rt. LC/MS was inconclusive. To the mixture was added 5 mL of 1N HCl, then the mixture was extracted with dichloromethane (3×15 mL) and dried with sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was again dissolved in 1,4 dioxane (3 mL) and 0.1 mL of 10N NaOH was added. The mixture was heated to 75° C. for 16.5 h, then was cooled to rt. To the mixture was added 10 mL of 1N HCl then the mixture was further diluted with 10 mL of water and it was extracted with dichloromethane (3×20 mL). The combined organic layers were dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in DMSO and was purified by prep HPLC (method 12, retention time: 10.2 minutes). The fractions containing the expected product were combined and concentrated under reduced pressure to give 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-carboxy-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)spiro[3.3]hept-5-ene-2,2-dicarboxylic acid (0.015 g, 0.021 mmol (based on 86% purity), 99% yield) as a white solid. LCMS: m/e 617.4 (M−H)−, 2.42 min (method 3). 1H NMR (500 MHz, acetic acid-d4) δ=5.93 (s, 1H), 5.58 (d, J=4.6 Hz, 1H), 4.76 (br. s., 1H), 4.62 (br. s., 1H), 3.08-2.99 (m, 1H), 2.81 (s, 4H), 2.69-2.59 (m, 2H), 1.71 (s, 3H), 2.40-0.80 (m, 37H).

1. temperaturewas cooled to rt
2. extractionthe mixture was extracted with dichloromethane (3×15 mL)
3. dry with materialdried with sodium sulfate
4. customThe drying agent was removed by filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. dissolutionThe residue was again dissolved in 1,4 dioxane (3 mL)
7. addition0.1 mL of 10N NaOH was added
8. temperatureThe mixture was heated to 75° C. for 16.5 h
9. temperaturewas cooled to rt
10. additionTo the mixture was added 10 mL of 1N HCl
11. additionthe mixture was further diluted with 10 mL of water and it
12. extractionwas extracted with dichloromethane (3×20 mL)
13. dry with materialThe combined organic layers were dried with sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. dissolutionThe residue was dissolved in DMSO
17. customwas purified by prep HPLC (method 12, retention time: 10.2 minutes)
18. additionThe fractions containing the expected product
19. concentrationconcentrated under reduced pressure