Reaktion #85724

Reaktionsgleichung

4-methyl-1H-imidazole

(R)—N—((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

K3PO4

→

(S)-1-(2,5-difluoro-4-(4-methyl-1H-imidazol-1-yl)phenyl)ethanamine

Ausbeute 143.4%

Lösungsmittel

EtOAc

water

toluene dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture was sealed
2. 2
   TemperaturThe reaction was cooled to room temperature
3. 3
   SonstigeThe reaction was sealed
4. 4
   Temperaturheated to 120° C. for 2 hours
5. 5
   TemperaturThe reaction mixture was then cooled to room temperature
6. 6
   ExtraktionThe aqueous layer was then extracted with EtOAc (2×20 mL)
7. 7
   EinengenThe combined organic was then concentrated
8. 8
   SonstigeThe residue was purified by silica gel chromatography (50% heptane in EtOAc to 10% MeOH in EtOAc)

Vorschrift

To a solution of di-tert-butyl(2′,4′,6′-triisopropyl-3,4,5,6-tetramethyl-[1,1′-biphenyl]-2-yl)phosphine (80 mg, 0.166 mmol) in toluene/dioxane (8 mL/2 mL) was added Pd2dba3 (60 mg, 0.066 mmol). The reaction mixture was sealed and heated to 120° C. and stirred for 5 minutes. The reaction was cooled to room temperature and 4-methyl-1H-imidazole (157 mg, 1.910 mmol), (R)—N—((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (500 mg, 1.470 mmol) and K3PO4 (624 mg, 2.94 mmol) was added to the reaction mixture. The reaction was sealed and heated to 120° C. for 2 hours. LCMS show complete conversion. The reaction mixture was then cooled to room temperature and diluted with EtOAc (20 mL) and water (10 mL). The aqueous layer was then extracted with EtOAc (2×20 mL). The combined organic was then concentrated. The residue was purified by silica gel chromatography (50% heptane in EtOAc to 10% MeOH in EtOAc) to give (S)-1-(2,5-difluoro-4-(4-methyl-1H-imidazol-1-yl)phenyl)ethanamine (500 mg). LCMS (B) m/z 342.6 (M+H)+

Quelle