Chloroacetyl chloride → Methyl 4-butyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylate

HRID 14199Notes

Reaction equation

HRID 14199 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[NH:12][CH2:13][CH2:14][CH2:15][CH3:16].C(=O)(O)[O-].[Na+].[CH3:22][C:23](CC(C)C)=[O:24].O.ClCC(Cl)=O>C(Cl)(Cl)Cl>[CH2:13]([N:12]1[C:3]2[C:2](=[CH:11][CH:10]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:4]=2)[NH:1][CH2:22][C:23]1=[O:24])[CH2:14][CH2:15][CH3:16]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 516892Sodium BicarbonateHCID 21086194Methyl 4-amino-3-(butylamino)benzoateHCID 22737866Isobutyl methyl ketone water

Product 1

HCID 21086199Methyl 4-butyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To an ice-cold, stirred solution of methyl 4-amino-3-(butylamino)benzoate (950 mg) and sodium bicarbonate (862 mg) in 1:1 isobutyl methyl ketone/water (20 mL) was added chloroacetyl chloride (0.41 mL), and the mixture was stirred for 1 h. The mixture was warmed to room temperature and refluxed for 14 h. The mixture was cooled to room temperature, diluted with chloroform, and separated. The organic layer was washed with water, and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:1 ethyl acetate/hexanes) afforded 850 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.89, 7.72, 6.80, 3.97, 3.88, 3.30-3.25, 1.68-1.58, 1.47-1.35, 0.94-0.88.

Workup

  1. temperaturerefluxed for 14 h
  2. temperatureThe mixture was cooled to room temperature
  3. customseparated
  4. washThe organic layer was washed with water, and brine
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (silica, 1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f4e0f794c7d34ee3b48fc68965cf8b7c
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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