Reaktion #172944

Reaktionsgleichung

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

Ausbeute 78.1%

Lösungsmittel

1,4-Dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated to reflux
2. 2
   TemperaturUpon heating
3. 3
   workup.DISSOLUTIONall solids dissolved
4. 4
   TemperaturAfter heating the mixture for 26 h
5. 5
   Einengenwas concentrated under reduced pressure
6. 6
   workup.ADDITIONThe residue was diluted with 100 mL of water
7. 7
   Extraktionwas extracted with dichloromethane (3×100 mL)
8. 8
   TrocknenThe combined organic layers were dried with sodium sulfate
9. 9
   SonstigeThe drying agent was removed by filtration
10. 10
    Einengenthe filtrate was concentrated under reduced pressure
11. 11
    SonstigeThe 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
    Einengenconcentrated under reduced pressure
14. 14
    EinengenA second batch of less-pure product was concentrated
15. 15
    Sonstigewas repurified
16. 16
    workup.ADDITIONthe same gradient The fractions containing the expected product

Vorschrift

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).

Quelle