Toluene → 4'-(4-Cyclopropyl-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluoro-biphenyl-2-carboxylic acid t-butyl ester

HRID 475673Notes

Reaction equation

HRID 475673 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH:26]=[O:27])=[C:24](Br)[N:23]=[C:22]3[O:29][CH2:30][CH3:31])=[C:16]([F:32])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:33]1(B(O)O)[CH2:35][CH2:34]1.C1(C)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH:26]=[O:27])=[C:24]([CH:33]4[CH2:35][CH2:34]4)[N:23]=[C:22]3[O:29][CH2:30][CH3:31])=[C:16]([F:32])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 1140Toluene2×HCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 510415724'-(4-Bromo-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

Product 1

HCID 592839094'-(4-Cyclopropyl-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluoro-biphenyl-2-carboxylic acid t-butyl esterYield 49.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×

Procedure

4′-(4-Bromo-2-ethoxy-5-formylimidazol-1-ylmethyl)-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester (2.6 g, 5.24 mmol), cyclopropylboronic acid (900 mg, 10.5 mmol) 1.0 M tricyclohexylphosphine in toluene (524 μL, 524 μmol), potassium phosphate (3.9 g, 18.4 mmol), and palladium acetate (118 mg, 524 mmol) were combined and dissolved in toluene (95.0 mL, 892 mmol). The mixture was stirred at room temperature under nitrogen for 20 minutes. Water (5.1 mL, 183 mmol) and potassium carbonate (2.5 g, 18.4 mmol) were then added and the mixture heated at 100° C. for 3 hours. Water (100 mL) was added and the layers separated. The organics were washed with water (50 mL) and saturated aqueous NaCl (50 mL), dried over Na2SO4, and the solvent evaporated. The product was purified by flash chromatography (0-40% EtOAc in hexanes to yield compound A (1.2 g).

Workup

  1. temperaturethe mixture heated at 100° C. for 3 hours
  2. customthe layers separated
  3. washThe organics were washed with water (50 mL) and saturated aqueous NaCl (50 mL)
  4. dry with materialdried over Na2SO4
  5. customthe solvent evaporated
  6. customThe product was purified by flash chromatography (0-40% EtOAc in hexanes

Sources & evidence

ORD record
ord-3ce10eb0a19b48a0901262ae37916824
Source dataset
uspto-grants-2014_01
Patent number
US08637562B2

Reaction notes

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