Potassium Carbonate → 4'-(4-Bromo-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

HRID 1810125Notes

Reaction equation

HRID 1810125 reaction equation
[Br:1][C:2]1[N:6]=[C:5]([O:7][CH2:8][CH3:9])[NH:4][C:3]=1[CH:10]=[O:11].[C:12]([O:16][C:17]([C:19]1[C:20]([C:25]2[CH:30]=[CH:29][C:28]([CH2:31]Br)=[C:27]([F:33])[CH:26]=2)=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:12]([O:16][C:17]([C:19]1[C:20]([C:25]2[CH:30]=[CH:29][C:28]([CH2:31][N:4]3[C:3]([CH:10]=[O:11])=[C:2]([Br:1])[N:6]=[C:5]3[O:7][CH2:8][CH3:9])=[C:27]([F:33])[CH:26]=2)=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 53375348Tert-butyl 4'-bromomethyl-3'-fluoro-biphenyl-2-carboxylateHCID 178467395HCID 178467395, compound

Product 1

HCID 510415724'-(4-Bromo-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluorobiphenyl-2-carboxylic acid t-butyl esterYield 15.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Bromo-2-ethoxy-3H-imidazole-4-carbaldehyde (10.0 g, 45.6 mmol), 4′-bromomethyl-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester (16.7 g, 45.6 mmol) and potassium carbonate (9.5 g, 68.5 mmol) were dissolved in DMF (200 mL) at 0° C. After 10 minutes, the mixture was allowed to warm to room temperature and was stirred overnight. The mixture was filtered and concentrated in vacuo. The concentrate was extracted with EtOAc (2×200 mL) and sat. aq. NaHCO3:water; 1:1 (150 mL). The combined organic fractions were dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was recrystallized from EtOH (20 mL) and water (40 mL) to afford a white solid. The filtrate was concentrated in vacuo and purified by silica gel chromatography (EtOAc:hexanes) to yield the title compound as a white solid (3.6 g).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated in vacuo
  3. extractionThe concentrate was extracted with EtOAc (2×200 mL) and sat. aq. NaHCO3
  4. dry with materialThe combined organic fractions were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was recrystallized from EtOH (20 mL) and water (40 mL)
  8. customto afford a white solid
  9. concentrationThe filtrate was concentrated in vacuo
  10. custompurified by silica gel chromatography (EtOAc:hexanes)

Sources & evidence

ORD record
ord-45c849424df34bcfb147612f25948eb9
Source dataset
uspto-grants-2013_01
Patent number
US08362061B2

Reaction notes

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