Hydrochloric Acid → HCID 22175934, compound

HRID 1797458Notes

Reaction equation

HRID 1797458 reaction equation
[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[C:9](=[O:17])[N:8]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:7]=1[C:23](OCC)=[O:24])[CH2:2][CH2:3][CH3:4].[OH-].[Na+].Cl.C(Cl)(=O)C(Cl)=O.[BH4-].[Na+]>O1CCCC1.C(O)C.CN(C)C=O.COCCOC.O>[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[C:9](=[O:17])[N:8]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:7]=1[CH2:23][OH:24])[CH2:2][CH2:3][CH3:4]

Participants

11

Reactant 5

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 4311764Sodium borohydrideHCID 22176065HCID 22176065, compound

Product 1

HCID 22175934HCID 22175934, compoundYield 57.1%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of ethyl 4-butoxy-6-fluoro-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (3.40 g, 9 mmol) in tetrahydrofuran (20 ml) and ethanol (20 ml) was added sodium hydroxide (1.08 g, 27 mmol). The obtained mixture was refluxed under heating for 12 h. The reaction mixture was poured into water and acidified with 1N hydrochloric acid 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 tetrahydrofuran (20 ml) and oxalyl chloride (0.9 ml, 10.8 mmol) and N,N-dimethylformamide (2 drops) were added thereto. The mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (20 ml). The obtained solution was added dropwise to a suspension of sodium tetrahydroborate (1.13 g, 30 mmol) in 1,2-dimethoxyethane (20 ml) at 0° C. The obtained mixture was stirred at 0° C. for 1 h. The reaction mixture was poured into 1N hydrochloric acid 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 4-butoxy-6-fluoro-3-hydroxymethyl-2-neopentyl-1(2H)-isoquinolinone (1.72 g, 57.1%) as crystals.

Workup

  1. temperatureThe obtained mixture was refluxed
  2. temperatureunder heating for 12 h
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in tetrahydrofuran (20 ml)
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. dissolutionthe residue was dissolved in tetrahydrofuran (20 ml)
  10. stirringThe obtained mixture was stirred at 0° C. for 1 h
  11. extractionextracted with ethyl acetate
  12. washThe extract was washed with brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography
  16. washthe component eluted earlier
  17. concentrationwas concentrated

Sources & evidence

ORD record
ord-f9399e4f199a4f59a80edbf028f1cd2c
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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