N-bromobutanimide → Methyl 1-bromo-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

HRID 1480941Notes

Reaction equation

HRID 1480941 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]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].[Br:23]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:23])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4]

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 86709142Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 89813003Methyl 1-bromo-4-hydroxy-7-phenoxyisoquinoline-3-carboxylateYield 58.1%

Reagents, catalysts & solvents 2

HCID 7187Benzoyl PeroxideCatalystHCID 5943Carbon TetrachlorideSolvent

Procedure

A mixture of 4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (6.0 g, 20.32 mmol), N-bromosuccinimide (3.80 g, 21.33 mmol) and benzoyl peroxide (246 mg, 1.01 mmol) in CCl4 was refluxed for 1 h. Solid was filtered off through a plug of silica gel. Filtrate was concentrated and purified by silica chromatography, eluting with EtOAc. All fractions contain the desired product was combined and concentrated. Residue was suspended in 150 mL of (3/1) MeOH/EtOAc and was refluxed for 1 h. After cooled, solid was collected, rinsed with MeOH and dried on vacuo to provide the title compound 4.42 g (11.8 mmol) in 58% yield as a white solid. 1H NMR in CDCl3, δ ppm: 11.7 (s, 1H), 8.36 (d, 1H, J=9.2 Hz), 7.63 (d, 1H, J=2.4 Hz), 7.55-7.10 (m, 6H), 4.06 (s, 3H).

Workup

  1. temperaturewas refluxed for 1 h
  2. filtrationSolid was filtered off through a plug of silica gel
  3. concentrationFiltrate was concentrated
  4. custompurified by silica chromatography
  5. washeluting with EtOAc
  6. concentrationconcentrated
  7. temperaturewas refluxed for 1 h
  8. temperatureAfter cooled
  9. customsolid was collected
  10. washrinsed with MeOH
  11. customdried on vacuo

Sources & evidence

ORD record
ord-534e2cba4604460b8c6b7a12463620e4
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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