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

HRID 14073Notes

Reaction equation

HRID 14073 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.[Cl-].[CH2:16]([N:19]([CH2:33][CH2:34][CH3:35])[C:20]([C:22]1[CH:23]=[C:24]([CH:29]=[C:30](I)[CH:31]=1)[C:25]([O:27][CH3:28])=[O:26])=[O:21])[CH2:17][CH3:18]>O1CCCC1.C(OCC)C.C(OCC)(=O)C.[Zn]>[CH2:33]([N:19]([CH2:16][CH2:17][CH3:18])[C:20]([C:22]1[CH:23]=[C:24]([CH:29]=[C:30]([C:6]2[N:5]([CH2:4][O:1][CH2:2][CH3:3])[CH:9]=[CH:8][N:7]=2)[CH:31]=1)[C:25]([O:27][CH3:28])=[O:26])=[O:21])[CH2:34][CH3:35]

Participants

9

Reactant 4

HCID 312ChlorideHCID 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 4

HCID 23994ZincCatalystHCID 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-a9cee3f20a0c4a74b9876bd5bcbfc97a
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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