Potassium Carbonate → Methyl 5-(2-(methoxymethyl)-1H-imidazol-5-yl)-2,4-dimethylbenzoate

HRID 1488112Notes

Reaction equation

HRID 1488112 reaction equation
I[C:2]1[NH:6][C:5]([CH2:7][O:8][CH3:9])=[N:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:16][C:17]1[CH:26]=[C:25]([CH3:27])[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:9][O:8][CH2:7][C:5]1[NH:6][C:2]([C:24]2[C:25]([CH3:27])=[CH:26][C:17]([CH3:16])=[C:18]([CH:23]=2)[C:19]([O:21][CH3:22])=[O:20])=[CH:3][N:4]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 59224686Methyl 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate2×HCID 900305675-Iodo-2-(methoxymethyl)-1H-imidazole2×

Product 1

HCID 90033625Methyl 5-(2-(methoxymethyl)-1H-imidazol-5-yl)-2,4-dimethylbenzoateYield 88%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Into a 100-mL three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 5-iodo-2-(methoxymethyl)-1H-imidazole (compound 230.4, 70 mg, 0.29 mmol) in dioxane (10 mL). Pd(dppf)Cl2 (22 mg, 0.029 mmol), a solution of potassium carbonate (160 mg, 1.16 mmol) in water (2 mL), methyl 2,4-dimethyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (compound 160.1, 168 mg, 0.58 mmol) were added to the reaction. The reaction mixture was stirred overnight at 90° C., then quenched with 10 mL of H2O. The aqueous phase was extracted with 3×10 mL of ethyl acetate and the combined organic layers were washed with 1×10 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:1) as eluent to furnish 70 mg (87%) of the title compound as a white solid.

Workup

  1. customInto a 100-mL three neck round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customquenched with 10 mL of H2O
  4. extractionThe aqueous phase was extracted with 3×10 mL of ethyl acetate
  5. washthe combined organic layers were washed with 1×10 mL of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:1) as eluent

Sources & evidence

ORD record
ord-914a2b9c8db34c89afc1bc810168905c
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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