Ethyl Acetate → 7-(4-Fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester

HRID 1618179Notes

Reaction equation

HRID 1618179 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Br)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].C([O-])(=O)C.[Na+].CCOC(C)=O>[Pd].CO>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[CH:10][C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 517045Sodium AcetateHCID 865954681-Bromo-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester

Product 1

HCID 667129667-(4-Fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl esterYield 97.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 1-Bromo-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (4.34 g, 10 mmol, see example A-75d), sodium acetate (984 mg, 12 mmol), Pd/C (2.0 g, 10 wt % Pd, 50 wt % water), EtOAc (400 ml) and MeOH (200 ml) was stirred under an H2-atmosphere at ambient pressure and temperature for 2.5 h before the mixture was filtered through a plug of celite. The celite was washed with EtOAc (500 ml). The combined organic phases were concentrated in vacuo. To the residue was added a half concentrated NaHCO3 solution (50 ml) and the mixture was extracted with CH2Cl2 (1×200 ml). The organic phase was dried over MgSO4 and concentrated in vacuo to yield the title compound as a tan oil (3.45 g); MS-(+)-ion M+1=356.1.

Workup

  1. filtrationwas filtered through a plug of celite
  2. washThe celite was washed with EtOAc (500 ml)
  3. concentrationThe combined organic phases were concentrated in vacuo
  4. additionTo the residue was added a half concentrated NaHCO3 solution (50 ml)
  5. extractionthe mixture was extracted with CH2Cl2 (1×200 ml)
  6. dry with materialThe organic phase was dried over MgSO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f9feb148e2314ac99360bd0d26ce5b3c
Source dataset
uspto-grants-2014_07
Patent number
US08765956B2

Reaction notes

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