1-Methylimidazole → Methyl 4-[3-(1-methylimidazol-2-yl)prop-1-en-1-yl]-2-(4-fluorophenyl)benzoate

HRID 1019037Notes

Reaction equation

HRID 1019037 reaction equation
C([Li])CCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.[Cu]C#N.[Cl-].[Li+].[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:33]=[C:32]([CH:34]=[CH:35][CH2:36]Br)[CH:31]=[CH:30][C:25]=2[C:26]([O:28][CH3:29])=[O:27])=[CH:20][CH:19]=1.C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>C1COCC1.O.[I-].[Zn+2].[I-]>[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:36][CH:35]=[CH:34][C:32]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([C:21]2[CH:20]=[CH:19][C:18]([F:17])=[CH:23][CH:22]=2)[CH:33]=1

Participants

10

Reactant 6

HCID 13901-MethylimidazoleHCID 6049Ethylenediaminetetraacetic AcidHCID 433294Lithium ChlorideHCID 54112501Methyl 2-(4-fluorophenyl)-4-(3-bromoprop-1-en-1-yl)benzoateHCID 178418339ButyllithiumHCID 178418546HCID 178418546, compound

Product 1

HCID 54337160Methyl 4-[3-(1-methylimidazol-2-yl)prop-1-en-1-yl]-2-(4-fluorophenyl)benzoateYield 71%

Reagents, catalysts & solvents 3

HCID 9883512zinc(II)iodideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

1H NMR (CDCl3, 400 MHz) δ: 3.65 (3H, m); 4.15 (2H, m); 6.1-6.2 and 6.4-6.7 (2H, m); 7-7.95 (7H, m). n-Butyl lithium (1.6 M solution in ether, 30 ml) was added at −78° C. and under argon atmosphere to a solution of N-methylimidazole (3.2 ml; 40 mmol). After stirring at −78° C. for 45 minutes, zinc iodide (14 g; 44 mmol) in solution in THF (100 ml) was added. The mixture was allowed to warm to ambient temperature for 1 hour, cooled down to −78° C., and a solution of copper (I) cyanide (0.72 g; 8 mmol) and lithium chloride (0.68 g; 1.6 mmol) in THF (10 ml) was then added at −78° C. followed by a solution of methyl 2-(4-fluorophenyl)-4-(3-bromoprop-1-en-1-yl)benzoate (7 g; 20 mmol) in THF (50 ml). The mixture was stirred at −78° C., for 30 minutes and for 1 hour 30 minutes at room temperature. After evaporation of the solvent, the residue was treated with EDTA (17 g; 44 mmol) in distilled water (50 ml) and extracted with dichloromethane. The organic layer was evaporated and purified by flash chromatography eluting with dichloromethane/ethanol (98/2) to give methyl 4-[3-(1-methylimidazol-2-yl)prop-1-en-1-yl]-2-(4-fluorophenyl)benzoate as a mixture of E and Z isomers. Yield: 71%

Workup

  1. temperatureto warm to ambient temperature for 1 hour
  2. temperaturecooled down to −78° C.
  3. stirringThe mixture was stirred at −78° C., for 30 minutes and for 1 hour 30 minutes at room temperature
  4. customAfter evaporation of the solvent
  5. extractionextracted with dichloromethane
  6. customThe organic layer was evaporated
  7. custompurified by flash chromatography
  8. washeluting with dichloromethane/ethanol (98/2)

Sources & evidence

ORD record
ord-92d67844ba3444a782f8c37d3c6bbac3
Source dataset
uspto-grants-2002_11
Patent number
US06486156B1

Reaction notes

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