1-(Ethoxymethyl)-1H-imidazole → Methyl 3-[(dipropylamino)carbonyl)-5-[1-(ethoxymethyl)-1H-imidazol-2-yl]benzoate

HRID 348865Notes

Reaction equation

HRID 348865 reaction equation
[O:1]([CH2:4][N:5]1[CH:9]=[CH:8][N:7]=[CH:6]1)[CH2:2][CH3:3].C([Li])CCC.[CH2:15]([N:18]([CH2:32][CH2:33][CH3:34])[C:19]([C:21]1[CH:22]=[C:23]([CH:28]=[C:29](I)[CH:30]=1)[C:24]([O:26][CH3:27])=[O:25])=[O:20])[CH2:16][CH3:17]>O1CCCC1.C(OCC)C.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:32]([N:18]([CH2:15][CH2:16][CH3:17])[C:19]([C:21]1[CH:22]=[C:23]([CH:28]=[C:29]([C:6]2[N:5]([CH2:4][O:1][CH2:2][CH3:3])[CH:9]=[CH:8][N:7]=2)[CH:30]=1)[C:24]([O:26][CH3:27])=[O:25])=[O:20])[CH2:33][CH3:34]

Participants

9

Reactant 3

HCID 130194491-(Ethoxymethyl)-1H-imidazoleHCID 21086179Methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoateHCID 178418339Butyllithium

Product 1

HCID 21086170Methyl 3-[(dipropylamino)carbonyl)-5-[1-(ethoxymethyl)-1H-imidazol-2-yl]benzoate

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a −70° C. stirred solution of 1-ethoxylmethylimidazole (J. Am. Chem. Soc. 1978, 100, 3918) (420 mg, 3.3 mmol) in tetrahydrofuran (10 mL) is added n-butyllithium (1.6 M in hexanes, 2.3 mL, 3.6 mmol). After 30 min, zinc chloride (9.9 mL of a 1 M solution in diethyl ether, 9.9 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is then added methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate (1.17 g, 3 mmol) followed by palladium(0) tetrakis(triphenylphosphine) (173 mg, 0.15 mmol). The reaction mixture is heated at reflux for 2 h. The reaction mixture is diluted with ethyl acetate (50 mL), washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 1–5% methanol/methylene chloride) provides the title compound in pure form. 1H NMR (300 MHz, CDCl3) δ 8.52 (s, 1H), 8.10 (s, 1H), 8.03 (s, 1H), 8.19 (s, 2H), 5.28 (s, 2H), 3.95 (s, 3H), 3.59 (q, J=7 Hz, 2H), 3.49 (m, 2H), 3.21 (m, 2H), 1.70 (m, 2H), 1.54 (m, 2H), 1.25 (t, J=7 Hz, 3H), 0.99 (m, 3H), 0.75 (m, 3H).

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 2 h
  3. washwashed with water, and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (silica gel, 1–5% methanol/methylene chloride)

Sources & evidence

ORD record
ord-084ca4bb1a7840c49f7acea6cc59804b
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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