Sodium hydride → 7-bromo-6-fluoro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one

HRID 1913123Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1913123
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][C:3]=1[F:13].[H-].[Na+].[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1>CC(N(C)C)=O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([CH2:22][C:21]3[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=3)[C:9]2=[O:12])=[CH:4][C:3]=1[F:13]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 598182537-Bromo-6-fluoro-1,2-dihydroisoquinolin-1-one

Produkt 1

HCID 598182577-bromo-6-fluoro-2-(4-methoxybenzyl)isoquinolin-1(2H)-oneAusbeute 116,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel2×

Versuchsvorschrift

9.66 g (39.9 mmol) of 7-Bbromo-6-fluoro-2H-isoquinolin-1-one (95) were dissolved in 180 ml of dimethyl acetamide and 1.92 g (48.0 mmol) of sodium hydride (60%) were added. After 1 h at room temperature a solution of 7.50 g (48.0 mmol) of 4-methoxy benzylchloride in 25 ml of dimethyl acetamide was added. The mixture was stirred at room temperature until complete conversion was achieved. The solvent was removed under reduced pressure, the residue was taken up in saturated sodium bicarbonate solution and extracted three times with dichloromethane. The organic layers were dried with magnesium sulfate and evaporated to yield 16.8 g of a dark oil as crude product, which was stirred in methanol. Filtration of the precipitate gave 6.56 g of the title compound as a yellow solid. The mother liquor was evaporated and the residue purified by preparative HPLC to yield additional 2.62 g of the desired product. Rt=1.71 min (Method C). Detected mass: 362.3/364.3 (M+H+).

Aufarbeitung

  1. customThe solvent was removed under reduced pressure
  2. extractionextracted three times with dichloromethane
  3. dry with materialThe organic layers were dried with magnesium sulfate
  4. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-3946d9c3b6e64458b4193941bfbdb2d4
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08609691B2

Notizen zur Reaktion

Wird geladen…