Reaktion #164542

Reaktionsgleichung

6-bromo-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one

N,N-dimethylethanolamine

toluene

dimethylzinc

dimethylzinc

→

6-methyl-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one

Ausbeute 34.2%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction mixture was stirred at 50° C. over the weekend
2. 2
   TemperaturAt this time, the reaction mixture was cooled to room temperature
3. 3
   Sonstigequenched with a saturated aqueous ammonium chloride solution
4. 4
   Extraktionextracted with ethyl acetate
5. 5
   workup.ADDITIONMethanol (0.5 mL) was added
6. 6
   Filtrationthe mixture was filtered
7. 7
   Sonstigethe layers were separated
8. 8
   SonstigeThe organic layers were absorbed onto silica gel

Vorschrift

A mixture of 6-bromo-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one (Example 128) (0.1 g, 0.28 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) dichloromethane complex (61.5 mg, 84.0 μmol) and N,N-dimethylethanolamine (14.1 μL, 140 μmol) in tetrahydrofuran (1.5 mL) under argon was treated with 1.2M dimethylzinc in toluene (280 μL, 0.33 mmol). The reaction mixture was stirred in a sealed vial at 50° C. overnight. At this time, the reaction was treated with additional dimethylzinc (0.14 mL). The reaction mixture was stirred at 50° C. over the weekend. At this time, the reaction mixture was cooled to room temperature, quenched with a saturated aqueous ammonium chloride solution and then extracted with ethyl acetate. Methanol (0.5 mL) was added, the mixture was filtered and the layers were separated. The organic layers were absorbed onto silica gel. Flash chromatography (12 g silica column, 0-40% ethyl acetate/hexanes) followed by trituration with methylene chloride afforded 6-methyl-3-(4-trifluoromethyl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one (14 mg, 17%) as white solid. 1H NMR (methanol-d4) δ ppm 7.76-7.86 (m, 4H), 7.69 (s, 1H), 7.28 (s, 1H), 6.95, (s, 1H), 2.28 (s, 3H). LC-MS calcd. for C15H12F3N2O [(M+H)+] 293, obsd. 293.1.

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