Hydrochloric Acid → HCID 54725311, compound

HRID 1797456Notes

Reaction equation

HRID 1797456 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[O:8][C:6](=O)[C:5]2=[CH:11][CH:12]=1.[CH2:13]([NH:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:14]([CH3:17])([CH3:16])[CH3:15].C(=O)([O-])[O-].[K+].[K+].C(I)C.C(O)C.[O-]CC.[Na+].Cl>O1CCCC1.O>[F:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6]([OH:8])=[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:18]([CH2:13][C:14]([CH3:15])([CH3:16])[CH3:17])[C:9]2=[O:10])=[CH:11][CH:12]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 675721,3-Isobenzofurandione, 5-fluoro-HCID 22176037HCID 22176037, compoundHCID 23706232Ethanol sodium ethoxide

Product 1

HCID 54725311HCID 54725311, compoundYield 31.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-fluorophthalic anhydride (8.31 g, 50 mmol) and ethyl 2-(neopentylamino)acetate (10.40 g, 60 mmol) in tetrahydrofuran (50 ml) was stirred at room temperature for 1 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (50 ml), and potassium carbonate (6.91 g, 50 mmol) and ethyl iodide (4.8 ml, 60 mmol) were added. The mixture was stirred at room temperature for 3 h. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in ethanol (50 ml) and 20% sodium ethoxide ethanol solution (34.04 g, 100 mmol) was added. The mixture was stirred at room temperature for 1 h. The reaction mixture was poured into 1N hydrochloric acid (150 ml) and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue, was purified by silica gel column chromatography and the component eluted earlier was concentrated to give ethyl 7-fluoro-4-hydroxy-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (5.12 g, 31.9%) as crystals.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (50 ml)
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in ethanol (50 ml)
  11. stirringThe mixture was stirred at room temperature for 1 h
  12. extractionextracted with ethyl acetate
  13. washThe extract was washed with brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue, was purified by silica gel column chromatography
  17. washthe component eluted earlier
  18. concentrationwas concentrated

Sources & evidence

ORD record
ord-dc9faeb38900411cbfb1c86d9629f225
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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