Hydrochloric Acid → HCID 22175601, compound

HRID 1797553Notes

Reaction equation

HRID 1797553 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:13]([C:24](OC)=[O:25])=[C:12]2[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+].Cl.C(Cl)(=O)C(Cl)=O.[BH4-].[Na+]>O1CCCC1.CO.CN(C)C=O.COCCOC.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:22])[CH3:23])[C:13]([CH2:24][OH:25])=[C:12]2[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

11

Reactant 5

HCID 313Hydrochloric Acid2×HCID 65578Oxalyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 4311764Sodium borohydrideHCID 22176273HCID 22176273, compound

Product 1

HCID 22175601HCID 22175601, compoundYield 32.2%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of methyl 6-benzyloxy-4-(3-fluorophenyl)-2-isobutyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (5.97 g, 13 mmol) in tetrahydrofuran (50 mL) and methanol (50 mL) was added an aqueous solution (10 mL) of lithium hydroxide monohydrate (1.64 g, 39 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 tetrahydrofuran (50 mL), and oxalyl chloride (1.0 mL, 12 mmol) and N,N-dimethylformamide (3 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 (30 mL). The obtained solution was added dropwise to a suspension of sodium tetrahydroborate (1.32 g, 35 mmol) in 1,2-dimethoxyethane (30 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 to give 6-benzyloxy-4-(3-fluorophenyl)-3-hydroxymethyl-2-isobutyl-1(2H)-isoquinolinone (1.39 g, 32.2%) 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 (50 mL)
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. dissolutionthe residue was dissolved in tetrahydrofuran (30 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

Sources & evidence

ORD record
ord-12e13322123948c3944f2287a11b4f05
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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