4-Amino-3-bromoquinoline

Uses

4-Amino-3-bromoquinoline is a useful research intermediate for the preparation of aminoquinolines.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 43, p. 4667, 2000 DOI: 10.1021/jm0002073

Synthesis

The general procedure for the synthesis of 3-bromo-4-aminoquinoline from 4-aminoquinoline was as follows: 34.6 g (240 mmol) of 4-aminoquinoline was added to a reaction flask and dissolved in 76 mL of glacial acetic acid. The reaction mixture was cooled to 0 °C and 42.2 g (264 mmol) of liquid bromine dissolved in 100 mL of glacial acetic acid was slowly added dropwise under stirring conditions. During the dropwise addition, a solid precipitate was observed to be generated, which was due to the low solubility of the product in acetic acid. After the dropwise addition was completed, the reaction mixture continued to be stirred at room temperature for 30 minutes. Subsequently, 1520 mL of ether was added to the reaction mixture and the precipitate was collected by filtration. The resulting precipitate was dissolved in 800 mL of water (most of the product was soluble in cold water and the remainder could be dissolved by heating to reflux). The solution was adjusted to alkaline with 1N aqueous sodium hydroxide, at which point a large amount of solid precipitated. The precipitate was collected by filtration, washed with 800 mL of water and dried in a vacuum oven under reduced pressure to give 44.16 g of 3-bromo-4-aminoquinoline, the product was off-white in 82% yield. The melting point was 200.6~201.7℃.

References

[1] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4667 - 4677
[2] Patent: CN105461623, 2016, A. Location in patent: Paragraph 0039-0041
[3] Journal fuer Praktische Chemie (Leipzig), 1894, vol. <2> 50, p. 239