Triethylamine → 3alpha-isocyanato-1-isopropenyl-5alpha,5beta,8,8,11alpha-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-ol

To a suspension of betulinic acid (10 g, 21.90 mmol) in 1,4-Dioxane (100 mL) was added triethylamine (9.16 mL, 65.7 mmol) and diphenyl phosphorazidate (7.08 mL, 32.8 mmol). The mixture was heated to reflux. Upon heating, all solids dissolved. After heating the mixture for 26 h, the mixture was cooled to rt and was concentrated under reduced pressure. The residue was diluted with 100 mL of water and was extracted with dichloromethane (3×100 mL). The combined organic layers were dried with sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography in silica gel using a 0-15% EtOAc in hexanes gradient and a Thomson 240 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure. A second batch of less-pure product was concentrated and was repurified using a Thomson 240 g column and the same gradient The fractions containing the expected product were combined with the first batch to give (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-isocyanato-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (7.76 g, 17.10 mmol, 78% yield) as a white solid. 1H NMR (400 MHz, chloroform-d) δ=4.75 (s, 1H), 4.67-4.62 (m, 1H), 3.20 (dt, J=11.3, 5.6 Hz, 1H), 2.55 (td, J=10.9, 5.9 Hz, 1H), 2.17-2.03 (m, 1H), 1.92-1.76 (m, 5H), 1.69 (s, 3H), 1.06 (s, 3H), 0.98 (s, 3H), 0.95 (s, 3H), 0.85 (s, 3H), 0.78 (s, 3H), 1.74-0.66 (m, 19H).

1. temperatureThe mixture was heated to reflux
2. temperatureUpon heating
3. dissolutionall solids dissolved
4. temperatureAfter heating the mixture for 26 h
5. concentrationwas concentrated under reduced pressure
6. additionThe residue was diluted with 100 mL of water
7. extractionwas extracted with dichloromethane (3×100 mL)
8. dry with materialThe combined organic layers were dried with sodium sulfate
9. customThe drying agent was removed by filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. customThe residue was purified by flash chromatography in silica gel using a 0-15% EtOAc in hexanes gradient
12. additionThe fractions containing the expected product
13. concentrationconcentrated under reduced pressure
14. concentrationA second batch of less-pure product was concentrated
15. customwas repurified
16. additionthe same gradient The fractions containing the expected product

ORDレコード

ord-3884eaf8b34b40be8c2bd3129a54742e

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08846647B2