Reaktion #80646

ord-95775d212b1a4e538d645c2f826c107f

Lösungsmittel

Reaktionsbedingungen

Temperatur
-78°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.STIRRINGthe reaction mixture was stirred at -78° C. for 1 hour
  2. 2
    Temperaturthe reaction mixture was warmed to room temperature
  3. 3
    workup.STIRRINGwas stirred overnight
  4. 4
    SonstigeThe reaction was quenched with 50 mL of 1N HCl
  5. 5
    Extraktionthe aqueous phase was extracted with ethyl acetate (3×60 mL)
  6. 6
    WaschenThe combined organic layers were washed with brine
  7. 7
    Trocknendried over MgSO4
  8. 8
    Filtrationfiltered
  9. 9
    Einengenconcentrated
  10. 10
    SonstigeThe crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35)

Vorschrift

To a solution of diisopropylamine (0.7 mL, 0.005 mol) in 9 mL of dry THF was added butyllithium (BuLi) (2.83 mL of 1.62M solution in hexane, 4.6 mmol) at 0° C. The solution was stirred at this temperature for 5 minutes and cooled to -78° C. with a dry ice/isopropanol bath. A solution of 2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine (Example 46) (1.46 g, 3.8 mmol) in 12 mL of dry THF was added over 10 minutes and the reaction mixture was stirred at -78° C. for 1 hour. (Iodomethyl)trimethylsilane (1.23 g, 57 mmol) was added dropwise and the reaction mixture was warmed to room temperature and was stirred overnight. The reaction was quenched with 50 mL of 1N HCl and the aqueous phase was extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35) to give 1.30 g of 2-methyl-3-[1-[4-[[2-(trimethylsilyl) ethyl]sulfonyl]phenyl]-4-(trifluoromethyl) -1H-imidazol-2-yl]pyridine as a white solid (74%): mp(DSC) 155°-157° C. Anal. Calc'd. for C21H24F3N3O2SSi: C, 53.94; H, 5.17; N, 8.99; S, 6.86. Found: C, 53.77; H, 4.94; N, 8.75; 6.98.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05616601uspto-grants-1997_04