Potassium Carbonate → 3,4-Dihydro-8-fluoro-2H-1,4-benzoxazine 2-ethyl carboxylate

HRID 1184351Notes

Reaction equation

HRID 1184351 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[OH:9].Br[CH:11]([CH2:17]Br)[C:12]([O:14]CC)=[O:13].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[F:8][C:4]1[C:3]2[O:9][CH2:12][CH2:11][NH:1][C:2]=2[CH:7]=[CH:6][CH:5]=1.[CH3:17][CH2:11][C:12]([O-:14])=[O:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 97945Ethyl 2,3-dibromopropionateHCID 6435622-Amino-6-fluorophenol

Product 1

HCID 866648003,4-Dihydro-8-fluoro-2H-1,4-benzoxazine 2-ethyl carboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 2-amino-6-fluorophenol (2 g, 8.3 mmol), of ethyl 2,3-dibromopropionate (1.46 mL, 9.96 mmol) and of K2CO3 (3.44 g, 24.9 mmol) in acetone (80 mL) is heated under reflux for 9 h 15 min. The mixture is cooled and filtered. The filtrate is vacuum concentrated, the residue dissolved in iced aqueous NaOH solution (1N, 10 mL) and extracted with ethyl ether. The ethereal phase is washed in water then saline water, dried over MgSO4 and concentrated under reduced pressure. The residue is purified by filtering though silica gel using dichoromethane as eluting solvent. The title compound is obtained in oil form (1.1 g, 59%).

Workup

  1. temperatureunder reflux for 9 h 15 min
  2. temperatureThe mixture is cooled
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionthe residue dissolved in iced aqueous NaOH solution (1N, 10 mL)
  6. extractionextracted with ethyl ether
  7. washThe ethereal phase is washed in water
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified
  11. filtrationby filtering though silica gel
  12. washas eluting solvent

Sources & evidence

ORD record
ord-77e74b4e96c2484eaeba885c3ebeba90
Source dataset
uspto-grants-2014_03
Patent number
US08669250B2

Reaction notes

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