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

HRID 2231139Notes

Reaction equation

HRID 2231139 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12](C(C)OCC)[CH:11]=[N:10][C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.CN([CH2:29][CH2:30]N(C)C)C.C([Li])C[CH2:36][CH3:37].CN(C)[C:41](=[O:43])[CH3:42].C(=O)(O)[O-:46].[Na+]>C1COCC1.C(OCC)C>[CH2:41]([O:43][CH:36]([N:10]1[C:9]([C:18]2[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][CH:19]=2)=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[N:12]=[C:11]1[C:29](=[O:46])[CH3:30])[CH3:37])[CH3:42]

Participants

8

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 31374DimethylacetamideHCID 516892Sodium BicarbonateHCID 536386915-(4-fluorophenyl)-4-(4-methylthiophenyl)-1-(1-methyl-1-ethoxymethyl)-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 184637511-[(1-Ethoxyethyl)-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-1H-imidazol-2-yl]ethanone

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1-(1-ethoxyethyl)-4-(4-fluorophenyl)-5-[4-(methylthio)phenyl]-1H-imidazole (Example 9, Step 2) (206 mg; 0.53 mmol) and TMEDA (324 mg; 1.65 mmol) in 3.0 mL of THF at −78° C. was added 0.28 ml of a 2.5 M solution of n-butyllithium in hexanes. After stirring for 15 minutes, 66 ml of N,N-dimethylacetamide (62.7 mg; 0.72 mmol) was added. After 30 minutes, the solution was slowly warmed to 25° C., then 2 ml of an aqueous solution of sodium bicarbonate was added, followed by dilution with 50 mL of diethyl ether. The solution was washed with 50 ml of a saturated solution of sodium bicarbonate and the organic extracts were dried (MgSO4) and filtered. The solvent was removed under reduced pressure to give 230 mg of a yellow oil, which was purified by flash chromatography (SiO2; 25% ethyl acetate/hexane) to yield 86 mg of the protected ketone as a slightly yellow oil (37%).

Workup

  1. waitAfter 30 minutes
  2. washThe solution was washed with 50 ml of a saturated solution of sodium bicarbonate
  3. dry with materialthe organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-02e32dbe870e4209b1008ce00304c845
Source dataset
uspto-grants-2002_07
Patent number
US06426360B1

Reaction notes

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