5-Ethynyl-1-methyl-1H-imidazole → Acetic acid 2,6-dimethoxy-3-(3-methyl-3H-imidazol-4-ylethynyl)-phenyl ester

HRID 2059619Notes

Reaction equation

HRID 2059619 reaction equation
[C:1]([O:4][C:5]1[C:6]([O:14][CH3:15])=[C:7](I)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])(=[O:3])[CH3:2].[C:16]([C:18]1[N:22]([CH3:23])[CH:21]=[N:20][CH:19]=1)#[CH:17]>CC#N.CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:15][O:14][C:6]1[C:7]([C:17]#[C:16][C:18]2[N:22]([CH3:23])[CH:21]=[N:20][CH:19]=2)=[CH:8][CH:9]=[C:10]([O:11][CH3:12])[C:5]=1[O:4][C:1](=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 33331065-Ethynyl-1-methyl-1H-imidazoleHCID 574219533-Acetoxy-2,4-dimethoxy-iodobenzene

Product 1

HCID 57421954Acetic acid 2,6-dimethoxy-3-(3-methyl-3H-imidazol-4-ylethynyl)-phenyl esterYield 56%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 3-acetoxy-2,4-dimethoxy-iodobenzene (250 mg, 0.776 mmol) and 5-ethynyl-1-methyl-1H-imidazole (100 mg, 1.09 mmol) in dry MeCN (3 ml) and dry NEt3 (1 ml) was added Pd(Ph3P)2Cl2 (20 mg, 3.7 mol %) and the reaction vessel was evacuated and backfilled with N2(g) three times. Copper (I) iodide (15 mg) was added and the reaction was heated to 60° C. and stirred overnight. The resulting dark solution was cooled, diluted with EtOAc and filtered through celite. The filtrate was concentrated onto silica-gel under reduced pressure and the solid residue was purified by flash chromatography (silica-gel, eluted with EtOAc) to give the product as a tan solid (130 mg, 56%). 1H-NMR (300 MHz, CDCl3) δ 7.45 (br s, 1H), 7.30 (d, J=8.7 Hz, 1H), 7.30 (br s, 1H), 6.68 (d, J=8.7 Hz, 1H), 3.94 (s, 3H), 3.83 (s, 3H), 3.71 (s, 3H), 2.33 (s, 3H).

Workup

  1. customthe reaction vessel was evacuated
  2. additionCopper (I) iodide (15 mg) was added
  3. temperatureThe resulting dark solution was cooled
  4. additiondiluted with EtOAc
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated onto silica-gel under reduced pressure
  7. customthe solid residue was purified by flash chromatography (silica-gel, eluted with EtOAc)

Sources & evidence

ORD record
ord-29b74652dae942c4b92c814e7c1f1e40
Source dataset
uspto-grants-2012_10
Patent number
US08278290B2

Reaction notes

Loading…