Butyl iodide → 6-Butoxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester

HRID 1833147Notes

Reaction equation

HRID 1833147 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][C:10]([O:17][CH3:18])=[C:11]([OH:16])[CH:12]=2)[CH:7]1[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:34](I)[CH2:35][CH2:36][CH3:37].C(OCC)(=O)C.CCCCCC>CN(C)C=O>[CH2:1]([O:3][C:4]([N:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][C:10]([O:17][CH3:18])=[C:11]([O:16][CH2:34][CH2:35][CH2:36][CH3:37])[CH:12]=2)[CH:7]1[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 10962Butyl iodideHCID 11430Potassium CarbonateHCID 210349376-hydroxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl esterHCID 21226206Ethyl acetate hexane

Product 1

HCID 695577576-Butoxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl esterYield 57.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of 6-hydroxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (840 mg, 2.28 mmol) in anhydrous N,N-dimethylformamide (25 mL) was added potassium carbonate (1.89 g, 13.6 mmol) and butyl iodide (0.78 mL, 6.83 mmol) dropwise. The reaction mixture was heated with stirring at 85° C. for 18 hrs. The solvent was evaporated and the residue was diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous phase was extracted with ethyl acetate (3×50 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 20% ethyl acetate/hexane) afforded 6-Butoxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (560 mg, 56% yield) as a colorless oil.

Workup

  1. temperatureThe reaction mixture was heated
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with ethyl acetate (50 mL) and water (50 mL)
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×50 mL)
  5. washThe combined extracts were washed with saturated aqueous sodium chloride solution (50 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3d788959662944a0a87094a4707898f2
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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