Dimethylformamide → 3-(1-cyano-1-methylethyl)-N-(3-hydroxy-4-methoxyphenyl)benzamide

HRID 2190409Notes

Reaction equation

HRID 2190409 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].CN(C)C=O.[NH2:20][C:21]1[CH:22]=[CH:23][C:24]([O:28][CH3:29])=[C:25]([OH:27])[CH:26]=1.C(N(C(C)C)C(C)C)C>C(Cl)(=O)C(Cl)=O.O>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([NH:20][C:21]1[CH:22]=[CH:23][C:24]([O:28][CH3:29])=[C:25]([OH:27])[CH:26]=1)=[O:11])([CH3:4])[CH3:5])#[N:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 743145-Amino-2-methoxyphenolHCID 81531DiisopropylethylamineHCID 571495383-(2-Cyanopropan-2-yl)benzoic acid

Product 1

HCID 673126173-(1-cyano-1-methylethyl)-N-(3-hydroxy-4-methoxyphenyl)benzamideYield 58.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 65578Oxalyl chlorideSolvent

Procedure

To a solution (20 mL) of 3-(1-cyano-1-methylethyl)benzoic acid (4.92 g, 26.0 mmol) in oxalyl chloride was added N,N-dimethylformamide (0.1 mL), and the mixture was stirred at room temperature for 30 min. Excess reagents were evaporated under reduced pressure, and the obtained residue was dissolved in tetrahydrofuran (20 mL), and 5-amino-2-methoxyphenol (4.17 g, 30.0 mmol) and N-ethyl-N-isopropylpropane-2-amine (6.46 g, 50.0 mmol) were successively added dropwise under ice-cooling. The reaction mixture was stirred at room temperature for 18 hr, poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (5 mL)/tetrahydrofuran (5 mL), 8N aqueous sodium hydroxide solution (1 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=5:1), and triturated with diethyl ether to give the title compound (4.70 g, 58%) as a pale-yellow solid.

Workup

  1. customExcess reagents were evaporated under reduced pressure
  2. dissolutionthe obtained residue was dissolved in tetrahydrofuran (20 mL)
  3. temperaturecooling
  4. stirringThe reaction mixture was stirred at room temperature for 18 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. dissolutionThe residue was dissolved in methanol (5 mL)/tetrahydrofuran (5 mL), 8N aqueous sodium hydroxide solution (1 mL)
  9. additionwas added under ice-
  10. temperaturecooling
  11. stirringthe mixture was stirred at room temperature for 18 hr
  12. additionThe reaction mixture was poured into water
  13. extractionthe mixture was extracted with ethyl acetate
  14. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  15. customthe solvent was evaporated under reduced pressure
  16. customThe residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=5:1)
  17. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-59b9d98a0ecb49cf94cc0daa18ef333d
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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