Acetaldehyde → 5-(Benzoxazol-2-yl)-1-cyclohexyl-2-methylbenzimidazole

HRID 74178Notes

Reaction equation

HRID 74178 reaction equation
[CH:1]1([NH:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[O:15][C:16]4[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=4[N:18]=3)=[CH:10][C:9]=2[N+:23]([O-])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H][H].[CH:28](=O)[CH3:29].CN(C)C=O.OOS([O-])=O.[K+].C(=O)([O-])[O-].[K+].[K+]>O.[C].[Pd].O1CCCC1>[O:15]1[C:16]2[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=2[N:18]=[C:14]1[C:11]1[CH:12]=[CH:13][C:8]2[N:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[C:28]([CH3:29])=[N:23][C:9]=2[CH:10]=1

Participants

10

Reactant 6

HCID 177AcetaldehydeHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 23707502Potassium hydroxy sulfiteHCID 674978972-(4-Cyclohexylamino-3-nitrophenyl)benzoxazoleHCID 178418361HCID 178418361, compound

Product 1

HCID 674980515-(Benzoxazol-2-yl)-1-cyclohexyl-2-methylbenzimidazoleYield 14%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(4-cyclohexylamino-3-nitrophenyl)benzoxazole (Working Example 16-1) (185 mg, 0.548 mmol) was added to a tetrahydrofuran (5 mL) solution including 10% palladium-carbon (50 mg), and a hydrogen atmosphere was substituted in the flask and this was stirred at room temperature for 5 hours. After the reaction was complete, this was filtered through Celite and the filtrate was concentrated. To a solution of the oil obtained in dimethylformamide (1.5 mL) was added a solution of acetaldehyde in dimethylformamide (approx. 2%, 1.35 mL, 0.586 mmol), water (0.1 mL), and oxone (117 mg, 0.190 mmol), and this was stirred at room temperature for 2.5 hours. After the reaction was complete, aqueous potassium carbonate solution was added, and this was extracted with ethyl acetate. The organic layer obtained was dried over anhydrous sodium sulfate, filtered, and concentrated to give an oil that was purified by silica gel column chromatography to yield the title compound (24.5 mg, 14% yield) as a light brown oil.

Workup

  1. filtrationthis was filtered through Celite
  2. concentrationthe filtrate was concentrated
  3. customTo a solution of the oil obtained in dimethylformamide (1.5 mL)
  4. stirringthis was stirred at room temperature for 2.5 hours
  5. extractionthis was extracted with ethyl acetate
  6. customThe organic layer obtained
  7. dry with materialwas dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give an oil that
  11. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-2fda9531f603427dbb1d81066a437318
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

Loading…