Reaktion #305085

Reaktionsgleichung

HCl

DCM MeOH

LiOH

product

Dimethyl 7′-(((11-azido-3,6,9-trioxaundecyl)oxy)carbamoyl)-5′-oxo-1′,5′-dihydrospiro[[1,3]dioxolane-2,4′-pyrrolo[2,3-f]quinoline]-2′,9′-dicarboxylate

HCl

→

7-(((11-Azido-3,6,9-trioxaundecyl)oxy)carbamoyl)-4,5-dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,9-dicarboxylic acid

Lösungsmittel

DCM

MeOH

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas kept at 45-47° C. in for 24 hours
2. 2
   EinengenThe solution was concentrated on a rotary evaporator
3. 3
   Sonstigeto remove THF
4. 4
   SonstigeThe resulting mixture was partitioned between EtOAc (100 mL) and saturated aqueous NaCl (50 mL)
5. 5
   SonstigeThe organic layer was separated
6. 6
   SonstigeThe organic solution was decanted from some aqueous droplets
7. 7
   SonstigeThe last two steps (standing and decanting)
8. 8
   SonstigeThe resulting EtOAc solution was then evaporated at reduced pressure
9. 9
   Sonstigeto give an orange gum
10. 10
    Sonstigeevaporated at reduced pressure twice
11. 11
    Sonstigeto give an orange foam which
12. 12
    Sonstigewas further dried in vacuo for 4 hours
13. 13
    Sonstigeto give red solution
14. 14
    SonstigeThe solution was partitioned between EtOAc (50 mL), water (5 mL) and saturated aqueous NaCl (5 mL)
15. 15
    SonstigeThe organic layer was separated
16. 16
    workup.WAITto stand for 15 minutes
17. 17
    SonstigeThe organic solution was decanted from some aqueous droplets
18. 18
    SonstigeEvaporation of solvent at reduced pressure
19. 19
    Sonstigegave a red gum
20. 20
    SonstigeThe gum was triturated with DCM
21. 21
    Sonstigethe resulting slurry was evaporated at reduced pressure
22. 22
    SonstigeThe resulting solid was triturated with DCM-hexanes (1:1)
23. 23
    Sonstigethe solvent was decanted from the red-brown solid
24. 24
    Sonstigethe solid was dried in vacuo
25. 25
    Sonstigeto afford 7 (94 mg 43%)

Vorschrift

A solution of the product from EXAMPLE 5 (6, 250 mg, 0.4 mMol) in THF (36 mL) was treated with 1N HCl (0.4 mL) was kept at 45-47° C. in for 24 hours. The reaction mixture was cooled to room temperature. TLC (DCM-MeOH 95:5) shows no 4 (Rf=0.75) and one major product (Rf=0.45). The solution was concentrated on a rotary evaporator to remove THF. The resulting mixture was partitioned between EtOAc (100 mL) and saturated aqueous NaCl (50 mL). The organic layer was separated and allowed to stand for 15 minutes. The organic solution was decanted from some aqueous droplets. The last two steps (standing and decanting) were repeated. The resulting EtOAc solution was then evaporated at reduced pressure to give an orange gum. The gum was dissolved in DCM (20 mL) and evaporated at reduced pressure twice to give an orange foam which was further dried in vacuo for 4 hours. The foam was dissolved in 0.5 M LiOH (3.4 mL, 1.7 mMol). The resulting black solution was stirred at room temperature for 24 hours. The reaction mixture was then acidified by dropwise addition of concentrated HCl (0.25 mL, 3 mMol) to give red solution. The solution was partitioned between EtOAc (50 mL), water (5 mL) and saturated aqueous NaCl (5 mL). The organic layer was separated and allowed to stand for 15 minutes. The organic solution was decanted from some aqueous droplets. Evaporation of solvent at reduced pressure gave a red gum. The gum was triturated with DCM and the resulting slurry was evaporated at reduced pressure. The resulting solid was triturated with DCM-hexanes (1:1), the solvent was decanted from the red-brown solid, and the solid was dried in vacuo to afford 7 (94 mg 43%). MS (AP− taken from a MeOH solution) 577 (M+MeOH-1), 545 (M−1).

Quelle