反応 #305085

反応方程式

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

溶媒

DCM

MeOH

THF

反応条件

後処理

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

実験手順

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).

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