Reaktion #171098

Reaktionsgleichung

2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

propargyl alcohol

pyrrolidine

→

3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)prop-2-yn-1-ol

Ausbeute 94.9%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas purged with argon
2. 2
   FiltrationThe reaction mixture was filtered through
3. 3
   Sonstigeto remove solids
4. 4
   WaschenThe filter agent was rinsed with EtOAc
5. 5
   Extraktionthe filtrate was extracted with EtOAc (3×75 mL)
6. 6
   WaschenThe combined extracts were washed with water and brine
7. 7
   Trocknendried over anhyd Na2SO4
8. 8
   Einengenconcentrated
9. 9
   Sonstigepurified by flash chromatography (80% EtOAc/hexanes)

Vorschrift

A mixture of 2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (0.79 g, 1.35 mmol), propargyl alcohol (122 μL, 2.03 mmol), pyrrolidine (169 μL, 2.03 mmol), CuI (26 mg, 0.13 mmol) and PdCl2(dppf)2 (50 mg, 0.07 mmol) in DMF (6.80 mL) was purged with argon and then heated to 80° C. for 3 h. The reaction mixture was filtered through to remove solids. The filter agent was rinsed with EtOAc and the filtrate was extracted with EtOAc (3×75 mL). The combined extracts were washed with water and brine, dried over anhyd Na2SO4, concentrated and purified by flash chromatography (80% EtOAc/hexanes) to get 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)prop-2-yn-1-ol (714 mg, 94%) as a yellow solid. MS (EI) m/z 557 (MH+).

Quelle