Chloroacetyl chloride → Methyl 8-bromo-4-butyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

HRID 14193

Reaction equation

HRID 14193 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([NH:13][CH2:14][CH2:15][CH2:16][CH3:17])[C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6].C(=O)(O)[O-].[Na+].[CH3:23][C:24](CC(C)C)=O.O.ClCC(Cl)=O>C(Cl)(Cl)Cl>[Br:1][C:2]1[C:11]2[O:12][CH2:24][CH2:23][N:13]([CH2:14][CH2:15][CH2:16][CH3:17])[C:10]=2[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 516892Sodium BicarbonateHCID 21086159Methyl 3-bromo-5-(butylamino)-4-hydroxybenzoateHCID 22737866Isobutyl methyl ketone water

Product 1

HCID 21086218Methyl 8-bromo-4-butyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To an ice-cold, stirred solution of Methyl 3-bromo-5-(butylamino)-4-hydroxybenzoate (440 mg) and sodium bicarbonate (280 mg) in 1:1 isobutyl methyl ketone/water (10 mL) was added chloroacetyl chloride (226 mg). The mixture was stirred for 1 h, warmed to room temperature, and heated at reflux for 14 h. The mixture was cooled to room temperature, diluted with chloroform, and the layer separated. The organic layer was washed with water, and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure to give a white solid: 1H NMR (300 MHz, CDCl3) δ 7.94, 7.62, 4.76, 3.98, 3.93, 1.65, 1.43, 0.97, which was used in the next step without further purification or characterization.

Workup

  1. temperatureheated
  2. temperatureat reflux for 14 h
  3. temperatureThe mixture was cooled to room temperature
  4. customthe layer separated
  5. washThe organic layer was washed with water, and brine
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a white solid
  10. custom1H NMR (300 MHz, CDCl3) δ 7.94, 7.62, 4.76, 3.98, 3.93, 1.65, 1.43, 0.97, which was used in the next step without further purification or characterization

Sources & evidence

ORD record
ord-2b1b9eee754e41cfa116c538002c58dc
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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