反応 #172944

反応方程式

betulinic acid

triethylamine

diphenyl phosphorazidate

→

(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

収率 78.1%

溶媒

1,4-Dioxane

反応条件

後処理

1. 1
   温度The mixture was heated to reflux
2. 2
   温度Upon heating
3. 3
   workup.DISSOLUTIONall solids dissolved
4. 4
   温度After heating the mixture for 26 h
5. 5
   濃縮was concentrated under reduced pressure
6. 6
   workup.ADDITIONThe residue was diluted with 100 mL of water
7. 7
   抽出was extracted with dichloromethane (3×100 mL)
8. 8
   乾燥The combined organic layers were dried with sodium sulfate
9. 9
   その他The drying agent was removed by filtration
10. 10
    濃縮the filtrate was concentrated under reduced pressure
11. 11
    その他The residue was purified by flash chromatography in silica gel using a 0-15% EtOAc in hexanes gradient
12. 12
    workup.ADDITIONThe fractions containing the expected product
13. 13
    濃縮concentrated under reduced pressure
14. 14
    濃縮A second batch of less-pure product was concentrated
15. 15
    その他was repurified
16. 16
    workup.ADDITIONthe same gradient The fractions containing the expected product

実験手順

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).

出典