Benzonitrile, 4-chloro-3-nitro- → 7-cyano-3,4-dihydroquinoxalin-2(1H)-one

HRID 1267152Notes

Reaction equation

HRID 1267152 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N+:10]([O-])=O.Cl.C[O:15][C:16](=O)[CH2:17][NH2:18].C([O-])(O)=O.[Na+]>CCO.CO.[Pd]>[C:6]([C:5]1[CH:4]=[C:3]2[C:2]([NH:18][CH2:17][C:16](=[O:15])[NH:10]2)=[CH:9][CH:8]=1)#[N:7]

Participants

7

Reactant 3

HCID 13655Benzonitrile, 4-chloro-3-nitro-HCID 122755Glycine methyl ester hydrochlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 107973017-cyano-3,4-dihydroquinoxalin-2(1H)-oneYield 112.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

To a solution of 4-chloro-3-nitrobenzonitrile (18.3 g, 100 mmol) and glycine methyl ester-hydrochloride (12.3 g, 100 mmol) in EtOH (150 mL) was added NaHCO3 (25.2 g, 300 mmol), and the resulting mixture was refluxed for 16 hours. The mixture was filtered and the filtrate was concentrated. The resulting residue was partitioned in EtOAc and water. The organic layer was neutralized with 1N HCl to pH 7 and then washed with brine, dried over MgSO4, and concentrated to give a crude (25 g). A solution of the crude was hydrogenated in MeOH (500 mL) in the presence of 10% Pd on carbon (1.5 g) at room temperature for 6 hours. The mixture was filtered and the filtrate was concentrated to give more of the same product (19.5 g, 100%). 1H NMR (DMSO-d6) δ 10.50 (s, 1H), 7.15 (dd, J=8.1 Hz, J=1.8 Hz, 1H), 6.94 (d, J=1.6 Hz, 1H), 6.93 (s, 1H), 6.68 (d, J=8.4 Hz, 1H), 3.90 (d, J=1.1 Hz, 2H); MS(CI) m/z 191 (M+NH4).

Workup

  1. temperaturethe resulting mixture was refluxed for 16 hours
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. customThe resulting residue was partitioned in EtOAc
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customto give a crude (25 g)
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-fefac3c7fb2c4d4f9872c3ff915491ed
Source dataset
uspto-grants-2003_04
Patent number
US06552042B2

Reaction notes

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