Phosphorus oxychloride → 7-Bromo-1-Chloroisoquinoline

HRID 551273Notes

Reaction equation

HRID 551273 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=O)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:15])=O.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[Cl:15])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 112761337-Bromoisoquinolin-1-ol

Product 1

HCID 65020247-Bromo-1-ChloroisoquinolineYield 61.9%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

7-Bromo-2H-isoquinolin-1-one (3.0 g, 13.4 mmol), phosphorus oxychloride (8.22 g, 53.6 mmol), and chloroform (25 mL) combined in a sealed tube and heated with stirring at 100° C. for 4 hours. Cooled to ˜60° C., poured into ice water (100 mL), neutralized carefully with saturated aqueous sodium hydrogencarbonate, extracted into methylene chloride and dried over magnesium sulfate. Flash column chromatography on silica gel gave the product as a pale cream solid (2.01 g, 8.3 mmol). 1H NMR (CDCl3) δ 8.51 (d, 1H), 8.30 (d, 1H), 7.82 (dd, 1H), 7.72 (d, 1H), 7.57 (dd, 1H). ESI MS (M+1)+: 242, 244, 246 (Br, Cl).

Workup

  1. temperatureheated
  2. temperatureCooled to ˜60° C.
  3. extractionextracted into methylene chloride
  4. dry with materialdried over magnesium sulfate

Sources & evidence

ORD record
ord-2264de8a5346429cb01dc3bcb5f89043
Source dataset
uspto-grants-2011_05
Patent number
US07947684B2

Reaction notes

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