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

HRID 14217

Reaction equation

HRID 14217 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6].C(=O)(O)[O-].[Na+].C[C:19]([CH2:21][CH:22]([CH3:24])C)=O.O.Cl[CH2:27][C:28](Cl)=[O:29]>C(Cl)(Cl)Cl>[CH2:24]([N:1]1[C:2]2[CH:3]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:9]=[CH:10][C:11]=2[O:12][CH2:27][C:28]1=[O:29])[CH2:22][CH2:21][CH3:19]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 10815Methyl 3-amino-4-hydroxybenzoateHCID 516892Sodium BicarbonateHCID 22737866Isobutyl methyl ketone water

Product 1

HCID 21086200Methyl 4-butyl-3-oxo-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-amino-4-hydroxybenzoate (3.0 g) and sodium bicarbonate (3.3 g) in 1:1 isobutyl methyl ketone/water (40 mL) was added chloroacetyl chloride (1.7 mL), and the mixture was stirred for 1 h. The mixture was warmed to room temperature and refluxed for 14 h, 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, 1:9 methanol/chloroform) afforded a phenoxazine 3.2 g as a white solid, which was used without further purification or characterization. To a solution of phenoxazine from step 1 (700 mg) and potassium carbonate (934 mg) in methanol (8 mL) was added bromobutane (1.8 mL), and the mixture was refluxed for 6 d. The mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and water. The organic layer washed with brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure to afforded 800 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.72-7.68, 7.02-6.99, 4.66, 4.00-3.92, 1.69-1.64, 1.46-1.38, 1.01-0.95.

Workup

  1. temperaturerefluxed for 14 h
  2. temperaturecooled 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, 1:9 methanol/chloroform)

Sources & evidence

ORD record
ord-7abefc4d35074a5d8e8dc1d7f37818a1
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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