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

HRID 1448468Notes

Reaction equation

HRID 1448468 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 slowly. 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 the filtrate was stripped of solvent. The residue was taken up in water and the solution was extracted with ether. The ether extract was dried (MgSO4) and the solvent was stripped. The residue was recrystallized from ethanol, eluted through a silica gel column using a 4:30:66 by volume mixture of tetrahydrofuran, ethyl acetate and hexane as eluent, and the product was recrystallized from ethanol, and then from ether, to give 2 as white crystals, m.p.: 85.5°-86.5°.

Workup

  1. temperatureThat mixture was heated
  2. additionwas added slowly
  3. additionhad been added
  4. temperatureThe mixture was refluxed for 21 hours
  5. filtrationSolids were filtered from the mixture
  6. extractionthe solution was extracted with ether
  7. extractionThe ether extract
  8. dry with materialwas dried (MgSO4)
  9. customThe residue was recrystallized from ethanol
  10. washeluted through a silica gel column
  11. additionby volume mixture of tetrahydrofuran, ethyl acetate and hexane as eluent
  12. customthe product was recrystallized from ethanol

Sources & evidence

ORD record
ord-b2effdb46b98439c85d67eea7afa0ba1
Source dataset
uspto-grants-1979_12
Patent number
US04180572

Reaction notes

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