N-bromobutanimide → 1-Bromo-8-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester

HRID 409205Notes

Reaction equation

HRID 409205 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)=[O:4].[Br:24]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([Br:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][C:17]1[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=1)=[O:4]

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 671104788-(4-Fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester

Product 1

HCID 866170631-Bromo-8-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl esterYield 55.5%

Reagents, catalysts & solvents 2

HCID 7187Benzoyl PeroxideCatalystHCID 5943Carbon TetrachlorideSolvent

Procedure

A mixture of 8-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester (1.21 g, 3.87 mmol), N-bromosuccinimide (723 mg, 4.06 mmol) and benzoyl peroxide (47 mg, 0.19 mmol) in carbon tetrachloride (20 mL) was refluxed for 4 h before it was cooled to room temperature and partitioned between dichloromethane and water. The organic layer was washed with saturated aqueous sodium bicarbonate, brine, and was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of dichloromethane and hexane to give the title compound as a pale yellow solid (843 mg): MS: (+) m/z 392.00, 393.93 (M+1, 79Br/81Br).

Workup

  1. temperaturewas refluxed for 4 h before it
  2. custompartitioned between dichloromethane and water
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate, brine
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel with a gradient of dichloromethane and hexane

Sources & evidence

ORD record
ord-a07e0172af914ab5bf9159b97b65b534
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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