Dimethylformamide → 2-benzyl-6-bromo-3-hydroxymethyl-4-phenyl-2H-isoquinolin-1-one

HRID 750132Notes

Reaction equation

HRID 750132 reaction equation
[CH2:1]([N:8]1[C:17]([C:18](O)=[O:19])=[C:16]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Br:27])[CH:14]=2)[C:9]1=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.CN(C=O)C>O1CCCC1>[CH2:1]([N:8]1[C:17]([CH2:18][OH:19])=[C:16]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Br:27])[CH:14]=2)[C:9]1=[O:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 230606482-benzyl-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid

Product 1

HCID 230609532-benzyl-6-bromo-3-hydroxymethyl-4-phenyl-2H-isoquinolin-1-oneYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-benzyl-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid (150 mg) in tetrahydrofuran (THF) (5 ml) were added oxalyl chloride (60 μl) and DMF (0.1 ml), and the mixture was stirred at room temperature for 1 hr. The solvent was concentrated under reduced pressure. A solution of the residue in THF (3 ml) was added dropwise to a suspension of sodium borohydride (39 mg) in 1,2-dimethoxyethane. The mixture was stirred under ice-cooling for 1 hr. and poured into 1N hydrochloric acid and the mixture was extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over magnesium sulfate. The solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1) to give the title compound (33 mg, 23%).

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. additionA solution of the residue in THF (3 ml) was added dropwise to a suspension of sodium borohydride (39 mg) in 1,2-dimethoxyethane
  3. stirringThe mixture was stirred under ice-
  4. temperaturecooling for 1 hr
  5. additionand poured into 1N hydrochloric acid
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationThe solvent was concentrated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-080554b177bb48be819921832bf6890d
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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