Hydrochloric Acid → HCID 54725296, compound

HRID 1797518Notes

Reaction equation

HRID 1797518 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.[CH:13]1([CH2:16][NH:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+].C(I)C.C(O)C.[O-]CC.[Na+].Cl>O1CCCC1.O>[CH:13]1([CH2:16][N:17]2[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:6]([OH:8])[C:5]3[C:4](=[CH:3][C:2]([F:1])=[CH:12][CH:11]=3)[C:9]2=[O:10])[CH2:14][CH2:15]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 675721,3-Isobenzofurandione, 5-fluoro-HCID 22175907Methyl [(cyclopropylmethyl)amino]acetateHCID 23706232Ethanol sodium ethoxide

Product 1

HCID 54725296HCID 54725296, compoundYield 28.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-fluorophthalic anhydride (24.99 g, 150 mmol) and ethyl 2-(cyclopropylmethylamino)acetate (23.58 g, 150 mmol) in tetrahydrofuran (200 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 (200 mL) and potassium carbonate (20.73 g, 150 mmol) and ethyl iodide (14.4 mL, 180 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 (300 mL) and a solution of 20% sodium ethoxide ethanol solution (102 g, 300 mmol) was added thereto. The mixture was stirred at room temperature for 1 h. The reaction mixture was poured into 1N hydrochloric acid (300 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 2-cyclopropylmethyl-7-fluoro-4-hydroxy-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (13.11 g, 28.6%) 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 (200 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 (300 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-c01d587e5809422183dbb34dc97fad11
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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