ChemicalBook CAS DataBase List 5-Bromoisoquinoline

5-Bromoisoquinoline synthesis

10synthesis methods

Product Name:5-Bromoisoquinoline
CAS Number:34784-04-8
Molecular formula:C9H6BrN
Molecular Weight:208.05

To mechanically stirred concd H2SO4 (42.5 mL) at 0 °C, isoquinoline (1; 5 mL, 42.5 mmol) was slowly added. The mixture was cooled to –25 °C, and NBS (9.83 g, 55.2 mmol) was added at such a rate that the reaction temperature was kept between –25 °C and –22 °C. The mixture was stirred at -22±1 °C for 2 h and at -18±1 °C for 3h. The mixture was then worked up as described above to give 6.16 g (72%) as a slightly off-white solid after chromatography; mp 81–82 °C. The solid was further purified by sublimation (75 °C/0.2 mmHg) to give 5-Bromoisoquinoline as a white powder[1].

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34784-04-8
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Yield:34784-04-8 81%

Reaction Conditions:

Stage #1:isoquinoline with N-Bromosuccinimide;sulfuric acid at -25 - 20;
Stage #2: with ammonia in water; pH=8 - 10 at 0;

Steps:

4 Synthesis of 5-bromoisoquinoline
Synthesis of 5-bromoisoquinoline Into a 250 mL 3-necked round-bottom flask, was placed H₂SO₄ (150 mL). To the above was added isoquinoline (17 g, 131.62 mmol) in several batches, while cooling to a temperature of 0° C. To the above was added NBS (29.2 g, 164.04 mmol) in several batches, while cooling to a temperature of -25-22° C. The resulting solution was allowed to react, with stirring, for 2 h while the temperature was maintained at -25° to -22° C. The resulting solution was allowed to react with stirring overnight, while the temperature was maintained at room temperature. The reaction progress was monitored by TLC (EtOAc/PE=1:5). The reaction mixture was then quenched by the adding 1000 mL of H₂O/ice. Adjustment of the pH to 8-10 was accomplished by the addition of NH₃.H₂O (30%). The resulting solution was extracted four times with 500 mL of EtOAc and the organic layers combined and dried over Na₂SO₄. The residue was purified by eluding through a column with a 1:5 EtOAc/PE solvent system. This resulted in 22.24 g (81%) of 5-bromoisoquinoline as a white solid.

References:

MEMORY PHARMACEUTICALS CORPORATION US2008/318941, 2008, A1 Location in patent:Page/Page column 22

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