Potassium Carbonate → methyl 1-methyl-2-phenyl-1H-imidazole-5-carboxylate

HRID 1397389Notes

Reaction equation

HRID 1397389 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:9]([CH3:10])[C:8](Br)=[N:7][CH:6]=1)=[O:4].[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CCO.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]>[CH3:10][N:9]1[C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][N:7]=[C:8]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 26343677Methyl 2-bromo-1-methyl-1H-imidazole-5-carboxylate

Product 1

HCID 58504255methyl 1-methyl-2-phenyl-1H-imidazole-5-carboxylateYield 81.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

Methyl-2-bromo-1-methyl-1H-imidazole-5-carboxylate (1 g, 4.56 mmol) and phenylboronic acid (0.67 g, 5.48 mmol) were dissolved in toluene-EtOH (80 mL, 5:3 v/v) and the solution was purged with argon for 10 min. K2CO3 (10 mL, 2M solution) and catalytic PdCl2(dppf) (82 mg, 0.12 mmol) were added and the reaction mixture was heated to 100° C. for 1 h. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water and washed with EtOAc. The aqueous layer was acidified to pH ˜6 using 1.5N HCl and the crude product was extracted with EtOAc. The combined extracts were dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 35-45% EtOAc in petroleum ether) to get methyl 1-methyl-2-phenyl-1H-imidazole-5-carboxylate (800 mg, yield 81%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.63-7.61 (m, 2H), 7.51-7.48 (m, 3H), 3.96 (s, 3H), 3.89 (s, 3H). MS (ESI) m/z: Calculated for C12H12N2O2: 216.09. found: 2168.8 (M+H)+.

Workup

  1. customthe solution was purged with argon for 10 min
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with water
  5. washwashed with EtOAc
  6. extractionthe crude product was extracted with EtOAc
  7. dry with materialThe combined extracts were dried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 35-45% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-8eeb754d28b648e582e66a4e71ee8085
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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