Sodium Carbonate → 4-(5-methylthiophen-2-yl)-1-trityl-1H-imidazole

HRID 1429110Notes

Reaction equation

HRID 1429110 reaction equation
IC1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.[CH3:26][C:27]1[S:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=1.[C:41]([O-])([O-])=O.[Na+].[Na+]>O.O1CCOCC1>[CH3:41][C:30]1[S:31][C:27]([C:26]2[N:3]=[CH:4][N:5]([C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:6]=2)=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 6182524-Iodo-1-tritylimidazoleHCID 118169404,4,5,5-Tetramethyl-2-(5-methylthiophen-2-yl)-1,3,2-dioxaborolane

Product 1

HCID 675105464-(5-methylthiophen-2-yl)-1-trityl-1H-imidazoleYield 83.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-iodo-1-trityl-1H-imidazole (7.95 g, 18.2 mmol), 5-methylthiophene-2-boronic acid pinacol ester (4.90 g, 21.9 mmol), Na2CO3 (7.66 g, 73.0 mmol) in H2O (20 mL) and dioxane (100 mL) was degassed (N2 bubbling). Pd(PPh3)4 (500 mg) was added and the mixture was heated to reflux for 4 h. The mixture was allowed to cool to room temperature and concentrated. The mixture was diluted with CH2Cl2 and H2O and the organic phase was separated. The aqueous phase was re-extracted (CH2Cl2) and the combined organics were washed (saturated aqueous NaCl), dried (MgSO4), filtered and concentrated to give a solid residue. The residue was purified by flash chromatography (EtOAc/CH2Cl2/hexanes 4:50:50 then 6:50:50 then 8:50:50) to give 4-(5-methylthiophen-2-yl)-1-trityl-1H-imidazole (6.15 g, 83%) as a colourless solid. 1H NMR (CDCl3, 400 MHz) δ2.46 (d, J=0.9 Hz, 3H), 6.62-6.65 (m, 1H), 6.94 (d, J=1.4 Hz, 1H), 6.99 (d, J=3.5 Hz, 1H), 7.15-7.21 (m, 6H), 7.31-7.37 (m, 9H), 7.41 (d, J=1.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ15.3, 75.5, 116.1, 121.7, 125.5, 128.1, 128.1, 129.8, 135.6, 136.4, 137.8, 138.9, 142.2; HRMS (EI) m/z 406.1496 C27H22N2S [M]+. requires 406.1498.

Workup

  1. customwas degassed (N2 bubbling)
  2. additionPd(PPh3)4 (500 mg) was added
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 4 h
  5. concentrationconcentrated
  6. additionThe mixture was diluted with CH2Cl2 and H2O
  7. customthe organic phase was separated
  8. extractionThe aqueous phase was re-extracted (CH2Cl2)
  9. washthe combined organics were washed (saturated aqueous NaCl)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a solid residue
  14. customThe residue was purified by flash chromatography (EtOAc/CH2Cl2/hexanes 4:50:50

Sources & evidence

ORD record
ord-7a3c942d60354a5687413c14726e0f58
Source dataset
uspto-grants-2015_01
Patent number
US08937303B2

Reaction notes

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