2-Amino-4-chlorophenol → ethyl 6-chloro-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

HRID 261185

Reaction equation

HRID 261185 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].Br[CH:11]([CH2:17]Br)[C:12]([O:14][CH2:15][CH3:16])=[O:13].C(=O)([O-])[O-]>CC(C)=O.C(=O)([O-])[O-].[K+].[K+]>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]2[O:9][CH:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:17][NH:1][C:2]=2[CH:7]=1

Participants

6

Reactant 3

HCID 72652-Amino-4-chlorophenolHCID 19660Carbonate Ion2×HCID 97945Ethyl 2,3-dibromopropionate

Product 1

HCID 3822578ethyl 6-chloro-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 11430Potassium CarbonateSolvent

Procedure

43.0 g of 2-amino-4-chlorophenol was dissolved in 500 ml of anhydrous acetone containing 42.0 g of anhydrous potassium carbonate. That mixture was heated to reflux temperature and 23.0 g of ethyl 2,3-dibromopropionate was added dropwise. In three additional portions each, additional ester and carbonate were added to the refluxing mixture until a total of 124 g of carbonate and 85.8 g of ester had been added. The mixture was refluxed for 21 hours. Solids were filtered from the mixture and washed with acetone. The filtrate was stripped of solvent and the residue was taken up in water. The water solution was extracted with ether. The ether extract was dried (MgSO4) and the solvent was stripped. The residue was eluted through a silica gel column using Solvent No. 3, the solvent was stripped and the residue was recrystallized from ethanol, then from ether to give ethyl 6-chloro-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate (3A), as white crystals, mp; 85.5°-86.5° C.

Workup

  1. temperatureThat mixture was heated
  2. additionwas added dropwise
  3. additionhad been added
  4. temperatureThe mixture was refluxed for 21 hours
  5. filtrationSolids were filtered from the mixture
  6. washwashed with acetone
  7. extractionThe water solution was extracted with ether
  8. extractionThe ether extract
  9. dry with materialwas dried (MgSO4)
  10. washThe residue was eluted through a silica gel column
  11. customthe residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-872d3778b28b4206ba26c6e12b12cb97
Source dataset
uspto-grants-1979_08
Patent number
US04164576

Linked notes

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