Dimethylformamide → 2-(1-(3-Chloro-6-fluoroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione

HRID 75386

Reaktionsgleichung

Reaktionsgleichung von HRID 75386
Br[CH:2]([C:4]1[C:13]([Cl:14])=[N:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:15])[CH:10]=2)[N:5]=1)[CH3:3].ClC1C(C(Cl)C)=NC2C(N=1)=CC(F)=CC=2.CN(C)C=O.[C:36]1(=[O:46])[NH:40][C:39](=[O:41])[C:38]2=[CH:42][CH:43]=[CH:44][CH:45]=[C:37]12.[K]>O>[Cl:14][C:13]1[C:4]([CH:2]([N:40]2[C:36](=[O:46])[C:37]3[C:38](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:39]2=[O:41])[CH3:3])=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([F:15])=[CH:8][CH:7]=2

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 24194345Phthalimide potassium saltHCID 866985202-(1-Bromoethyl)-3-chloro-6-fluoroquinoxalineHCID 866985223-Chloro-2-(1-chloroethyl)-6-fluoroquinoxaline

Produkt 1

HCID 866985212-(1-(3-Chloro-6-fluoroquinoxalin-2-yl)ethyl)isoindoline-1,3-dioneAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a mixture of 2-(1-bromoethyl)-3-chloro-6-fluoroquinoxaline (57.17 g, 197.5 mmol) containing 3-chloro-2-(1-chloroethyl)-6-fluoroquinoxaline (48.39 g, 197.5 mmol) in N,N-dimethylformamide (700.0 ml, 197.5 mmol) was added potassium phthalimide (91.43 g, 493.6 mmol) at rt and the mixture was stirred at rt for 1 h. After 1 h, to the mixture was added water (2 L). The mixture was extracted with DCM (500 mL×3). The combined organic layers were washed with brine (1 L×1), dried over MgSO4, filtered, and concentrated under reduced pressure to give a red liquid. The red liquid was filtered though a plug of silica (5.5 inch diameter×5 inch height), and eluented with 20% of EtOAc in hexane, then 30% of EtOAc in hexane, and then 100% of EtOAc as eluent to give two fractions. Second fraction, desired product 2-(1-(3-chloro-6-fluoroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione (53.367 g, 75.97% yield) as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.25 (dd, J=9.4, 5.9 Hz, 1H), 7.81-7.95 (m, 6H), 5.86 (q, J=6.8 Hz, 1H), 1.86 (d, J=7.0 Hz, 3H). Mass Spectrum (ESI) m/e=356.0 (M+1).

Aufarbeitung

  1. waitAfter 1 h
  2. extractionThe mixture was extracted with DCM (500 mL×3)
  3. washThe combined organic layers were washed with brine (1 L×1)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a red liquid
  8. filtrationThe red liquid was filtered though a plug of silica (5.5 inch diameter×5 inch height)
  9. custom30% of EtOAc in hexane, and then 100% of EtOAc as eluent to give two fractions

Quellen und Nachweise

ORD-Eintrag
ord-831bfac601c449d1959af70e801fd977
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835432B2

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