Dimethylformamide → 6-[2-(2-methoxyethoxy)ethoxy]-2H-isoquinolin-1-one

HRID 1271229Notes

Reaction equation

HRID 1271229 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16]C(O)=O)[CH:12]=[CH:13][CH:14]=1.S(Cl)(Cl)=O.C[N:25](C)[CH:26]=[O:27].[N-]=[N+]=[N-].[Na+]>O.O1CCOCC1>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:12](=[CH:13][CH:14]=1)[C:26](=[O:27])[NH:25][CH:16]=[CH:15]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 693742173-{3-[2-(2-Methoxyethoxy)ethoxy]phenyl}Acrylic Acid

Product 1

HCID 184529226-[2-(2-methoxyethoxy)ethoxy]-2H-isoquinolin-1-oneYield 32%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

To 3-{3-[2-(2-methoxyethoxy)ethoxy]phenyl}acrylic acid (10.7 g, 40.4 mmol) was added thionyl chloride (60 mL) and N,N-dimethylformamide (5 mL) and the reaction solution was refluxed under nitrogen atmosphere for 15 h. The reaction solution was dried, concentrated and the resulting oil was taken up in 1,4-dioxane (25 mL) and added dropwise during 15 min to a solution of sodium azide (7.87 g, 121 mmol) in water/dioxane (28 mL, 1:1) at 0° C. The suspension was stirred 30 min at 0° C., after which the precipitate was filtered off and washed with ethyl acetate. The filtrate was extracted with ethyl acetate (3×150 mL) and the combined organic layer was washed with water (75 mL) and brine (75 mL), dried over sodium sulphate and filtered. The azide containing solution volume was reduced in vacuo, diphenyl ether (20 mL) was added and the remaining ethyl acetate was removed in vacuo. The diphenyl ether solution of the azide was added dropwise during 20 min to hot diphenyl ether (65 mL, 230° C.) and the obtained solution was heated 2 h at reflux (˜260° C.) and then left stirring at room temperature over night. Hexane was added to the reaction solution and the product precipitated out as a black oil. The oil was pre-absorbed on silica gel and purified by flash chromatography (solvent gradient:methanol/methylene chloride, 2:98→4:96) giving, after concentration and drying of the appropriate fractions, 3.4 g (32% yield) of the title compound as a yellow solid. MS (AP+) m/z 264 (M++1).

Workup

  1. temperaturethe reaction solution was refluxed under nitrogen atmosphere for 15 h
  2. customThe reaction solution was dried
  3. concentrationconcentrated
  4. filtrationafter which the precipitate was filtered off
  5. washwashed with ethyl acetate
  6. extractionThe filtrate was extracted with ethyl acetate (3×150 mL)
  7. washthe combined organic layer was washed with water (75 mL) and brine (75 mL)
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. additionwas added
  11. customthe remaining ethyl acetate was removed in vacuo
  12. additionThe diphenyl ether solution of the azide was added dropwise during 20 min to hot diphenyl ether (65 mL, 230° C.)
  13. temperaturethe obtained solution was heated 2 h
  14. temperatureat reflux (˜260° C.)
  15. waitleft
  16. stirringstirring at room temperature over night
  17. additionHexane was added to the reaction solution
  18. customthe product precipitated out as a black oil
  19. customThe oil was pre-absorbed on silica gel
  20. custompurified by flash chromatography (solvent gradient:methanol/methylene chloride, 2:98→4:96)
  21. customgiving
  22. concentrationafter concentration

Sources & evidence

ORD record
ord-9c802c554862454dad71d4830eeb4d01
Source dataset
uspto-grants-2007_04
Patent number
US07205314B2

Reaction notes

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