Ammonium → 5-Bromoisoquinoline

HRID 880496Notes

Reaction equation

HRID 880496 reaction equation
N([O-])=O.[Na+].[CH:5]1[C:14]2[C:9](=[C:10](N)[CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][N:6]=1.[BrH:16].[NH4+]>O>[Br:16][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:9]=1[CH:8]=[CH:7][N:6]=[CH:5]2

Participants

6

Reactant 4

HCID 223AmmoniumHCID 260Hydrogen Bromide2×HCID 707665-AminoisoquinolineHCID 23668193Sodium Nitrite

Product 1

HCID 7364875-BromoisoquinolineYield 53.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium nitrite (2.15 g, 31.21 mmol) in water (2 mL) was added to a solution of isoquinolin-5-ylamine (3.0 g, 20.80 mmol) in aqueous 46% hydrogen bromide (9.98 g, 124.84 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min then a solution of cuprous bromide (3.58 g, 24.96 mmol) in aqueous 46% hydrogen bromide (9.98 g, 124.84 mmol) was added and the reaction was allowed to warm to ambient temperature and stirred for 2 h. The resulting mixture was basified with aqueous ammonium and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulphate and concentrated to afford the crude compound. Purification by column chromatography over silica gel (100-200 mesh) with 20% ethyl acetate in petroleum ether as eluent afforded 5-bromoisoquinoline (2.3 g, 53%) as a pale yellow solid.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 2 h
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationconcentrated
  7. customto afford the crude compound
  8. customPurification by column chromatography over silica gel (100-200 mesh) with 20% ethyl acetate in petroleum ether as eluent

Sources & evidence

ORD record
ord-66bb2666cf8b4c5491b8a34a6b49fd8f
Source dataset
uspto-grants-2015_03
Patent number
US08993574B2

Reaction notes

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