Lithium iodide → 2((4-(4-fluorophenyl)-1H-imidazol-1-yl)methyl)-2-methylcyclohexane-1,3-dione

HRID 1876912Notes

Reaction equation

HRID 1876912 reaction equation
[CH3:1][CH:2]1[C:7](=[O:8])[CH2:6][CH2:5][CH2:4][C:3]1=[O:9].[I-].[Li+].C1CCN2C(=NCCC2)CC1.Cl.Cl[CH2:25][N:26]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[N:28]=[CH:27]1>C(OCC)(=O)C.CCCCCCC.O.C1COCC1>[F:37][C:34]1[CH:35]=[CH:36][C:31]([C:29]2[N:28]=[CH:27][N:26]([CH2:25][C:2]3([CH3:1])[C:7](=[O:8])[CH2:6][CH2:5][CH2:4][C:3]3=[O:9])[CH:30]=2)=[CH:32][CH:33]=1

Participants

9

Reactant 4

HCID 66321Lithium iodideHCID 709452-Methyl-1,3-cyclohexanedioneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 67447079HCID 67447079, compound

Product 1

HCID 461802502((4-(4-fluorophenyl)-1H-imidazol-1-yl)methyl)-2-methylcyclohexane-1,3-dioneYield 60%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 2-methylcyclohexane-1,3-dione (10 g, 79 mmol), lithium iodide (26 g, 194 mmol), and anhydrous THF (300 mL) cooled in a water bath was added 1,8-diazabicyclo[5.4.0]-7-undecene (14 mL, 94 mmol) dropwise under nitrogen. The mixture was stirred at RT for 40 min before 1-(chloromethyl)-4-(4-fluorophenyl)-1H-imidazole hydrochloride (9.8 g, 40 mmol) was added in one portion. The reaction mixture was stirred at RT for 3 hr and at 60° C. for 2 hr. After the mixture was cooled, water (250 mL) and heptane (250 mL) were added. The aqueous layer was separated and extracted with ethyl acetate (2×250 mL). The combined organic solutions were washed with 16% aqueous potassium carbonate solution (3×50 mL), dried (Na2SO4), and concentrated. Silica gel flash chromatography (20-100% ethyl acetate in hexanes) gave 2((4-(4-fluorophenyl)-1H-imidazol-1-yl)methyl)-2-methylcyclohexane-1,3-dione (7.1 g, 24 mmol, 60% yield) as a solid. MS found: (M+H)+=301.4.

Workup

  1. additionwas added in one portion
  2. temperatureAfter the mixture was cooled
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×250 mL)
  5. washThe combined organic solutions were washed with 16% aqueous potassium carbonate solution (3×50 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-afb10af51009448cb68e4aaf7015a277
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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