Potassium Carbonate → 5-(Benzoxazol-2-yl)-2-methyl-1-(3-phenylpropyl)benzimidazole

HRID 74231

Reaction equation

HRID 74231 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][C:3]=1[N+:17]([O-])=O.C(=O)([O-])[O-].[K+].[K+].[C:26]1([CH2:32][CH2:33][CH2:34][NH2:35])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[H][H].CO[C:40](OC)(OC)[CH3:41]>C(O)C.CO.[C].[Pd].O>[O:9]1[C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[N:12]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]2[N:35]([CH2:34][CH2:33][CH2:32][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:40]([CH3:41])=[N:17][C:3]=2[CH:4]=1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 15050Trimethyl orthoacetateHCID 162593-PhenylpropylamineHCID 219909702-(4-Fluoro-3-nitrophenyl)benzoxazoleHCID 178418361HCID 178418361, compound

Product 1

HCID 674980645-(Benzoxazol-2-yl)-2-methyl-1-(3-phenylpropyl)benzimidazoleYield 17.8%

Reagents, catalysts & solvents 4

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a suspension of 2-(4-fluoro-3-nitrophenyl)benzoxazole (see Working Example 15-2) (300 mg, 1.16 mmol) in ethanol (5 mL) was added potassium carbonate (176 mg, 1.28 mmol) and 3-phenylpropylamine (189 mg, 1.39 mmol), and this was heated to reflux for 3 hours. After the reaction was complete, this was cooled to room temperature, water was added, and the precipitated crystals were filtered, washed with water and then dried. To a tetrahydrofuran solution (5 mL) of the crystals obtained was added 10% palladium-carbon (50 mg). A hydrogen atmosphere was substituted in the flask, and this was stirred at room temperature for 6 hours. After the reaction was complete, this was filtered through Celite and the filtrate was concentrated. The residue obtained was dissolved in methanol (5 mL), and to this was added 1,1,1-trimethoxyethane (108 mg, 0.896 mmol), and this was heated to reflux for 6 hours. After the reaction was complete, this was concentrated, and the residue obtained was purified by silica gel column chromatography to yield the title compound (58.5 mg, 14% yield) as white crystals.

Workup

  1. temperaturethis was heated
  2. temperatureto reflux for 3 hours
  3. filtrationthe precipitated crystals were filtered
  4. washwashed with water
  5. customdried
  6. customTo a tetrahydrofuran solution (5 mL) of the crystals obtained
  7. filtrationthis was filtered through Celite
  8. concentrationthe filtrate was concentrated
  9. customThe residue obtained
  10. temperaturethis was heated
  11. temperatureto reflux for 6 hours
  12. concentrationthis was concentrated
  13. customthe residue obtained
  14. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-195f30aa87854e2c8186d29248fe96ca
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Linked notes

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