4-Hydroxybenzaldehyde → 4-{3-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)-2-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)methyl]propoxy}benzaldehyde

HRID 539404Notes

Reaction equation

HRID 539404 reaction equation
[CH3:1][Si:2]([CH3:31])([CH3:30])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:12][CH:13]([CH2:16][C:17]1[N:18]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:19]=[CH:20][N:21]=1)[CH2:14][OH:15].O[C:33]1[CH:40]=[CH:39][C:36]([CH:37]=[O:38])=[CH:35][CH:34]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O.O1CCCC1>[CH3:31][Si:2]([CH3:1])([CH3:30])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:12][CH:13]([CH2:16][C:17]1[N:18]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:27])[CH3:29])[CH:19]=[CH:20][N:21]=1)[CH2:14][O:15][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=[O:38])=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 689541183-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)-2-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)methyl]-1-propanol

Product 1

HCID 866301044-{3-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)-2-[(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)methyl]propoxy}benzaldehydeYield 58.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a tetrahydrofuran (2 mL) solution of the compound (120 mg) produced in Example 18 and a 4-hydroxybenzaldehyde (31 mg), triphenylphosphine (81 mg) and diethylazodicarboxylate (175 μL) were added in this order. The reaction solution was stirred at room temperature for 15 hours. To the reaction solution, water (20 mL) was added. The aqueous layer was extracted twice with ethyl acetate (50 mL). The combined organic layer was washed with saturated sodium chloride solution (50 mL) and then dried over anhydrous magnesium sulfate. After removing the anhydrous magnesium sulfate by filtration, the filtrate was concentrated. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=80:20→0:100→ethyl acetate:methanol:28% aqueous ammonia=100:0:0→80:20:2) to obtain the title compound (85 mg) having the following physical properties.

Workup

  1. extractionThe aqueous layer was extracted twice with ethyl acetate (50 mL)
  2. washThe combined organic layer was washed with saturated sodium chloride solution (50 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customAfter removing the anhydrous magnesium sulfate
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=80:20→0:100→ethyl acetate:methanol:28% aqueous ammonia=100:0:0→80:20:2)

Sources & evidence

ORD record
ord-14b3d9234a8444228c8ea6817a75d1aa
Source dataset
uspto-grants-2014_10
Patent number
US08871210B2

Reaction notes

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