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

HRID 1802929Notes

Reaction equation

HRID 1802929 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 68.9%

Procedure

5-Bromo-2-ethoxy-3H-imidazole-4-carbaldehyde (6.0 g, 27.4 mmol), 4′-bromomethyl-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester (10.0 g, 27.4 mmol), and potassium carbonate (3.8 g, 27.4 mmol) were dissolved in DMF (383 mL, 4950 mmol) and the mixture was stirred at room temperature for 2 hours. The reaction was quenched with water, and the mixture was extracted with EtOAc, washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated. The resulting material was purified by silica gel chromatography (0-30% EtOAc:hexanes) to yield intermediate (16a) (9.5 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 was extracted with EtOAc
  3. washwashed with saturated aqueous NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting material was purified by silica gel chromatography (0-30% EtOAc:hexanes)

Sources & evidence

ORD record
ord-7361051c0d18467d9305121a0c09c860
Source dataset
uspto-grants-2013_01
Patent number
US08349875B2

Reaction notes

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