3-Aminophenol → 3-(1-cyano-1-methylethyl)-N-(3-hydroxyphenyl)benzamide

HRID 2190386Notes

Reaction equation

HRID 2190386 reaction equation
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=O)([CH3:5])[CH3:4])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[CH:23]=[C:24]([OH:28])[CH:25]=[CH:26][CH:27]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.O>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=1)=[O:11])([CH3:4])[CH3:5])#[N:2]

Participants

8

Reactant 4

HCID 115683-AminophenolHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 571495383-(2-Cyanopropan-2-yl)benzoic acid

Product 1

HCID 573868253-(1-cyano-1-methylethyl)-N-(3-hydroxyphenyl)benzamideYield 96.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 3-(1-cyano-1-methylethyl)benzoic acid (10 g, 52.8 mmol) produced in Example A7(ii) in tetrahydrofuran (100 mL) were added N,N-dimethylformamide (4 drops) and oxalyl chloride (6.28 mL, 72.0 mmol), and the mixture was stirred at room temperature for 1.5 hr. The solvent was evaporated under reduced pressure to give a residue. To a solution of 3-aminophenol (5.24 g, 48.0 mmol) in tetrahydrofuran (40 mL) was added a suspension of sodium hydrogencarbonate (6.05 g, 72.0 mmol) in water (60 mL), and the mixture was stirred vigorously at room temperature. To this mixture was added dropwise a solution of the residue obtained above in tetrahydrofuran (60 mL) under ice-cooling, and the mixture was stirred at room temperature for 5 hr. The aqueous layer of the reaction mixture was separated, and the organic layer was diluted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and decolorized with activated carbon. The insoluble material was filtered off through a pad filled with two layers of silica gel and celite. The solvent was evaporated under reduced pressure, and the obtained solid was washed with ethyl acetate-hexane mixture to give the title compound (13.03 g, 96%) as a white powder.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customto give a residue
  3. stirringthe mixture was stirred vigorously at room temperature
  4. additionTo this mixture was added dropwise a solution of the residue
  5. temperaturecooling
  6. stirringthe mixture was stirred at room temperature for 5 hr
  7. customThe aqueous layer of the reaction mixture was separated
  8. additionthe organic layer was diluted with ethyl acetate
  9. washwashed with saturated brine
  10. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  11. filtrationThe insoluble material was filtered off through a pad
  12. additionfilled with two layers of silica gel and celite
  13. customThe solvent was evaporated under reduced pressure
  14. washthe obtained solid was washed with ethyl acetate-hexane mixture

Sources & evidence

ORD record
ord-2ad4181620344d19bfa93dae8de4ba49
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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