Triethylamine → 2,3-Dihydro-1,4-benzodioxin-5-amine

HRID 1750148Notes

Reaction equation

HRID 1750148 reaction equation
C([N:3]([CH2:6][CH3:7])CC)C.[O:8]1[CH2:13][CH2:12][O:11][C:10]2C(C(O)=O)=C[CH:16]=[CH:17][C:9]1=2.C(Cl)(=O)OCC.[N-]=[N+]=[N-].[Na+]>CC(C)=O.O>[O:8]1[CH2:13][CH2:12][O:11][C:10]2[C:6]([NH2:3])=[CH:7][CH:16]=[CH:17][C:9]1=2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 781842,3-Dihydro-1,4-benzodioxin-5-carboxylic acid

Product 1

HCID 117883872,3-Dihydro-1,4-benzodioxin-5-amineYield 70%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent3×HCID 962WaterSolvent2×

Procedure

Triethylamine in acetone was added dropwise to the solution of 2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylic acid (360 mg, 2 mmol) in water and acetone at 0° C. To the mixture was added ethyl carbonochloridate in acetone slowly. The mixture was stirred for 4 h then a solution of NaN3 (196 mg, 3.02 mmol) in water was added dropwise. The reaction mixture was stirred for 1 h then it was poured into ice water and extracted with Et2O. The combined organic extracts were washed with brine, dried with MgSO4, and concentrated in vacuo. The residue was dissolved in anhydrous toluene and the mixture was heated on a steam bath until nitrogen evolution had ceased. The toluene was then removed in vacuo and 20% aq HCl (4 mL) was added and the solution was heated to reflux and stirred overnight. The reaction was concentrated under reduced pressure. The residue was dissolved in water, made strongly alkaline by the addition of 40% aq NaOH, then extracted with Et2O. The combined organic extracts were washed with brine, dried by MgSO4, and purified by flash chromatography on silica gel column (PE:EtOAc=5:1) to give 2,3-dihydrobenzo[b][1,4]dioxin-5-amine (intermediate 60) (270 mg, 70%). HPLC: 99%, RT 1.214 min. MS (ESI) m/z 152.1 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred for 1 h
  2. extractionextracted with Et2O
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried with MgSO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in anhydrous toluene
  7. temperaturethe mixture was heated on a steam bath until nitrogen evolution
  8. customThe toluene was then removed in vacuo and 20% aq HCl (4 mL)
  9. additionwas added
  10. temperaturethe solution was heated
  11. temperatureto reflux
  12. stirringstirred overnight
  13. concentrationThe reaction was concentrated under reduced pressure
  14. dissolutionThe residue was dissolved in water
  15. additionmade strongly alkaline by the addition of 40% aq NaOH
  16. extractionextracted with Et2O
  17. washThe combined organic extracts were washed with brine
  18. dry with materialdried by MgSO4
  19. custompurified by flash chromatography on silica gel column (PE:EtOAc=5:1)

Sources & evidence

ORD record
ord-15a06fafee9a46ba9ab7b9ea9da52725
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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