Dichloromethane → 2-((1S)-1-(8-Fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 1019791Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1019791
O[O:2][S:3]([O-:5])=O.[K+].[F:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1SC)[C:14]([C@@H:26]([N:28]1[C:36](=[O:37])[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:29]1=[O:38])[CH3:27])=[CH:13]2.[CH2:39](Cl)Cl>>[F:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[S:3]([CH3:39])(=[O:5])=[O:2])[C:14]([C@@H:26]([N:28]1[C:36](=[O:37])[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:29]1=[O:38])[CH3:27])=[CH:13]2

Komponenten

4

Edukt 3

HCID 6344Dichloromethane2×HCID 23707502Potassium hydroxy sulfiteHCID 866984982-((1S)-1-(8-fluoro-2-(2-(methylthio)-phenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

Produkt 1

HCID 866984992-((1S)-1-(8-Fluoro-2-(2-(methylsulfonyl)phenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dioneAusbeute 97 %

Versuchsvorschrift

To 70 mL of DCM was added 13.56 g (1.2 g/1 mmol of substrate) of wet Montmorillonite (˜0.2 g H2O/1 g of clay), and oxone (17.37 g, 28.2 mmol)1. To this suspension was added a solution of 2-((1S)-1-(8-fluoro-2-(2-(methylthio)-phenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione (5.0 g, 11.3 mmol) dissolved in DCM (10 mL). The slurry was stirred at rt for 72 h and then filtered through a fritted funnel. The solids were washed with DCM (˜600 mL) and the filtrates were concentrated under vacuum to give 2-((1S)-1-(8-fluoro-2-(2-(methylsulfonyl)phenyl)-3-quinolinyl)ethyl)-1H-isoindole-1,3(2H)-dione 7.11 g (97%) as a light yellow solid. The proton NMR reflects a 59/41 ratio of atropisomers at 25° C. 1H-NMR (500 MHz, CDCl3) δ ppm 8.86 (s, 0.59H), 8.79 (s, 0.41H), 8.26 (d, J=7.8 Hz, 0.41H), 8.04 (d, J=7.8 Hz, 0.59H), 7.89-7.36 (series of m, 9.6H), 7.20 (d, J=7.6 Hz, 0.41H), 5.70 (q, J=7.1 Hz, 0.59H), 5.54 (q, J=7.3 Hz, 0.41H), 3.19 (s, 1.75H), 3.15 (s, 1.25H), 1.98 (d, J=7.3 Hz, 1.75H), 1.85 (d, J=7.1 Hz, 1.25H). Mass Spectrum (ESI) m/e=475.0 (M+1).

Aufarbeitung

  1. filtrationfiltered through a fritted funnel
  2. washThe solids were washed with DCM (˜600 mL)
  3. concentrationthe filtrates were concentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-8214a6bec35c43118511353dcfa1a739
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716290B2

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