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

HRID 919332Notes

Reaction equation

HRID 919332 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 4

HCID 6228DimethylformamideHCID 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 72.5%

Procedure

5-Bromo-2-ethoxy-3H-imidazole-4-carbaldehyde (15.0 g, 68.5 mmol), 4′-bromomethyl-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester (25.0 g, 68.5 mmol) and potassium carbonate (9.5 g, 68.5 mmol) were dissolved in DMF (958 mL, 12.4 mol) and was stirred at room temperature for 2 hours. The reaction was quenched with water, and the mixture extracted with EtOAc, washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated in vacuo. The mixture was purified by silica gel chromatography (0-30% EtOAc:hexanes) to yield intermediate (15a) (25 g). MS m/z: [M+H+] calcd for C24H24BrFN2O4, 503.3. found 503.2. 1H-NMR (CDCl3): 9.57 (1H, s), 7.80 (1H, d), 7.48 (2H, m), 7.27 (1H, s), 7.11 (1H, t), 7.01 (2H, d), 5.47 (2H, s), 4.33 (2H, q), 1.41 (3H, t), 1.24 (9H, s).

Workup

  1. customThe reaction was quenched with water
  2. extractionthe mixture extracted with EtOAc
  3. washwashed with saturated aqueous NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe mixture was purified by silica gel chromatography (0-30% EtOAc:hexanes)

Sources & evidence

ORD record
ord-22d807b9adfd40eba326e3ae438a184a
Source dataset
uspto-grants-2016_03
Patent number
US09273008B2

Reaction notes

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