Hydrochloric Acid → HCID 22176339, compound

HRID 1797520Notes

Reaction equation

HRID 1797520 reaction equation
[CH2:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13](F)[CH:14]=2)[C:9](=[O:17])[N:8]([CH2:18][CH:19]2[CH2:21][CH2:20]2)[C:7]=1[C:22]([O:24]CC)=[O:23])[CH2:2][CH2:3][CH3:4].[OH-:27].[Na+].Cl.[H-].[Na+]>O1CCCC1.C(O)C.C(O)C1C=CC=CC=1.O>[CH2:9]([O:27][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:17])[N:8]([CH2:18][CH:19]1[CH2:21][CH2:20]1)[C:7]([C:22]([OH:24])=[O:23])=[C:6]2[O:5][CH2:1][CH2:2][CH2:3][CH3:4])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 22176051HCID 22176051, compound

Product 1

HCID 22176339HCID 22176339, compoundYield 138.7%

Reagents, catalysts & solvents 4

HCID 244Benzyl AlcoholSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of ethyl 4-butoxy-2-cyclopropylmethyl-6-fluoro-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (9.03 g, 25 mmol) in tetrahydrofuran (30 mL) and ethanol (30 mL) was added sodium hydroxide (3.00 g, 75 mmol). The obtained mixture was refluxed under heating for 12 h. The reaction mixture was poured into water, 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 benzyl alcohol (20 mL) and the obtained solution was added dropwise to a solution of sodium hydride (5.0 g, 125 mmol)(60% in oil) in benzyl alcohol (20 mL). The obtained mixture was stirred at 150° C. for 12 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 obtained crystals were recrystallized from tetrahydrofuran-diisopropyl ether to give 6-benzyloxy-4-butoxy-2-cyclopropylmethyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylic acid (7.31 g, 69.4%) 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 benzyl alcohol (20 mL)
  8. extractionextracted with ethyl acetate
  9. washThe extract was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained crystals were recrystallized from tetrahydrofuran-diisopropyl ether

Sources & evidence

ORD record
ord-b6fe2557c6ed4709be266cfe6d39f7e0
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

Loading…