N,N,N',N'-Tetramethylethylenediamine → 1-[1-(1-Ethoxyethyl)-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-1h-imidazol-2-yl]-2,2,2-trifluoroethanone

HRID 2231137Notes

Reaction equation

HRID 2231137 reaction equation
[CH2:1]([O:3][CH:4]([N:6]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)=[C:9]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[N:8]=[CH:7]1)[CH3:5])[CH3:2].CN(CCN(C)C)C.C([Li])CCC.CON(C)[C:42](=[O:47])[C:43]([F:46])([F:45])[F:44]>C1COCC1.C(OCC)C>[CH2:1]([O:3][CH:4]([N:6]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)=[C:9]([C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[N:8]=[C:7]1[C:42](=[O:47])[C:43]([F:46])([F:45])[F:44])[CH3:5])[CH3:2]

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 27823822,2,2-Trifluoro-N-methoxy-N-methylacetamideHCID 178289901-(1-ethoxyethyl)-4-(4-fluorophenyl)-5-(4-methylthiophenyl)-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 184637341-[1-(1-Ethoxyethyl)-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-1h-imidazol-2-yl]-2,2,2-trifluoroethanone

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of 1-(1-Ethoxyethyl)-4-(4-fluorophenyl)-5-[4-(methyl-thio)phenyl]-1H-imidazole (Example 83 Step 1) (403.8 mg; 1.04 mmol) and TMEDA (582.7 mg; 5.01 mmol) in 6 ml of THF at −78° C. was added 1.23 ml of 2.5 M n-butyllithium in hexanes. After stirring for 15 minutes, a solution of N-methoxy-N-methyltrifluoracetamide, (167 mg; 1.41 mmol) in 1 ml of THF was added. The solution was warmed to 25° C. over one hour. The reaction was diluted with diethyl ether and washed with a saturated, aqueous, solution of sodium bicarbonate. The organic extracts were dried (MgSO4), filtered and evaporated under reduced pressure to give the crude product, which was purified by flash chromatography (SiO2; 25% ethyl acetate/hexane) to give 81 mg of 1-[1-(1-ethoxyethyl)-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-1H-imidazol-2-yl]-2,2,2-trifluoroethanone which was used directly in the next step.

Workup

  1. washwashed with a saturated, aqueous, solution of sodium bicarbonate
  2. dry with materialThe organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customto give the crude product, which
  6. customwas purified by flash chromatography (SiO2; 25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-cd5db3e21b884d4da8e5019c3f983597
Source dataset
uspto-grants-2002_07
Patent number
US06426360B1

Reaction notes

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