Potassium Carbonate → (S)-methyl 2,4-dimethyl-5-(5-(tetrahydrofuran-2-yl)-1H-imidazol-2-yl)benzoate

HRID 541403Notes

Reaction equation

HRID 541403 reaction equation
Cl.[C:2]([C:5]1[C:6]([CH3:16])=[CH:7][C:8]([CH3:15])=[C:9]([CH:14]=1)[C:10]([O:12][CH3:13])=[O:11])(=[NH:4])[NH2:3].Br[CH2:18][C:19]([C@@H:21]1[CH2:25][CH2:24][CH2:23][O:22]1)=O.C(=O)([O-])[O-].[K+].[K+]>CC#N>[CH3:15][C:8]1[CH:7]=[C:6]([CH3:16])[C:5]([C:2]2[NH:3][C:19]([C@@H:21]3[CH2:25][CH2:24][CH2:23][O:22]3)=[CH:18][N:4]=2)=[CH:14][C:9]=1[C:10]([O:12][CH3:13])=[O:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 45080892(S)-2-bromo-1-(tetrahydrofuran-2-yl)ethanone2×HCID 68288602Methyl 5-carbamimidoyl-2,4-dimethylbenzoate hydrochloride2×

Product 1

HCID 68288792(S)-methyl 2,4-dimethyl-5-(5-(tetrahydrofuran-2-yl)-1H-imidazol-2-yl)benzoateYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To a round-bottom flask was added a solution of methyl 5-carbamimidoyl-2,4-dimethylbenzoate hydrochloride (compound 2.5, 1.30 g) in CH3CN (30 mL). (S)-2-bromo-1-(tetrahydrofuran-2-yl)ethanone (compound 257.2, 1.92 g, 9.95 mmol) and potassium carbonate (4.20 g, 30.4 mmol) were added to the reaction. The resulting solution was stirred for 3 days at 75° C. under nitrogen. After cooling to ambient temperature, the solids were removed by filtration. The filtrate was concentrated in vacuo and diluted with 30 mL of H2O. The aqueous phase was extracted with 3×50 mL of ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate, then concentrated in vacuo. The mixture was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:2) as eluent to yield 400 mg (25%) of (S)-methyl 2,4-dimethyl-5-(5-(tetrahydrofuran-2-yl)-1H-imidazol-2-yl)benzoate as a light yellow solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe solids were removed by filtration
  3. concentrationThe filtrate was concentrated in vacuo
  4. additiondiluted with 30 mL of H2O
  5. extractionThe aqueous phase was extracted with 3×50 mL of ethyl acetate
  6. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe mixture was purified

Sources & evidence

ORD record
ord-bdcb68a5f25c4cd9a0c197f0ed201bc8
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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