Diisopropylamine → 2-methyl-3-[1-[4-[[2-(trimethylsilyl)ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine

HRID 1166385Notes

Reaction equation

HRID 1166385 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[C:19]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][CH:30]=3)[CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[N:24]=2)=[CH:18][CH:17]=[CH:16][N:15]=1.I[CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42]>C1COCC1>[CH3:13][C:14]1[C:19]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH2:38][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])(=[O:37])=[O:36])=[CH:31][CH:30]=3)[CH:22]=[C:23]([C:25]([F:27])([F:28])[F:26])[N:24]=2)=[CH:18][CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 77877(Iodomethyl)trimethylsilaneHCID 10786069Pyridine,2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1h-imidazol-2-yl]-HCID 178418339Butyllithium

Product 1

HCID 229977722-methyl-3-[1-[4-[[2-(trimethylsilyl)ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridineYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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 44) (1.46 g, 3.8 mmol) in 12 mL of dry THF was added over 10 minutes and the reaction mixture was stirred at −780° 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 1 N 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; S, 6.98.

Workup

  1. stirringthe reaction mixture was stirred at −780° C. for 1 hour
  2. temperaturethe reaction mixture was warmed to room temperature
  3. stirringwas stirred overnight
  4. customThe reaction was quenched with 50 mL of 1 N HCl
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×60 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35)

Sources & evidence

ORD record
ord-d7b73e8d99394d4f9a3f590dc99b6dd1
Source dataset
uspto-grants-2003_09
Patent number
US06613789B2

Reaction notes

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