Triethylamine → 1-Ethyl-4-(3-methoxy-phenylethynyl)-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 2220463Notes

Reaction equation

HRID 2220463 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:12][CH3:13])[CH:8]=[C:9](I)[CH:10]=1)=[O:5])[CH3:2].CCN(CC)CC.[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1)#[CH:22]>C(#N)C.[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:12][CH3:13])[CH:8]=[C:9]([C:22]#[C:21][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6407531-Ethynyl-3-methoxybenzeneHCID 68698718Ethyl-4-iodo-1H-pyrrole-2-carboxylic acid ethyl ester

Product 1

HCID 686983271-Ethyl-4-(3-methoxy-phenylethynyl)-1H-pyrrole-2-carboxylic acid ethyl esterYield 86.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent2×

Procedure

Argon was gently bubbled to a mixture of ethyl-4-iodo-1H-pyrrole-2-carboxylic acid ethyl ester (4.1 g, 14 mmol), CuI (0.14 g, 0.76 mmol), Et3N (40 ml, 287 mmol) and tetrakis(triphenylphosphosphine)palladium (0) (0.64 g, 0.554 mmol) in ACN (20 mL) over 5 minutes. A prepared solution of 1-ethynyl-3-methoxy-benzene (2.03 g, 15.4 mmol) in ACN (5 mL) was added into it and the new mixture was reflux under Nitrogen for 3 hours. The resulting brown colored reaction mixture was cooled to room temperature and concentrated in vacuo. The concentrate was diluted with water and extracted with ether. The combined ether extracts were washed with saturated aqueous solution of NH4Cl, brine, dried (MgSO4) and filtered. Evaporation and purification by flash chromatography on silica gel (Hexane/EtOAc 9.7/0.3) gave the title compound as a yellow brownish oil (3.6 g, 84% yield), 1H NMR (400 MHZ, CDCl3) δ 1.31-1.34 (t, 3H), 1.38-1.40 (t, 3H), 3.78 (s, 3H), 4.25-4.27 (q, 2H), 4.30-4.33 (q, 2H), 6.83 (m, 1H), 6.89 (m, 1H), 7.06 (m, 3H), 7.19 (m, 1H), MS m/e (M+H)+ 298.1.

Workup

  1. temperaturethe new mixture was reflux under Nitrogen for 3 hours
  2. concentrationconcentrated in vacuo
  3. additionThe concentrate was diluted with water
  4. extractionextracted with ether
  5. washThe combined ether extracts were washed with saturated aqueous solution of NH4Cl, brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customEvaporation and purification by flash chromatography on silica gel (Hexane/EtOAc 9.7/0.3)

Sources & evidence

ORD record
ord-ee1264f2f38b4de285078153a26f57f0
Source dataset
uspto-grants-2008_08
Patent number
US07417047B2

Reaction notes

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