4-Bromo-1-chloro-2-nitrobenzene Chemical Properties

Melting point:

0°C

Boiling point:

0°C

Density 

2.035 g/cm3(Temp: 16 °C)

Flash point:

0°C

storage temp. 

Sealed in dry,Room Temperature

solubility 

soluble in Methanol

form 

powder to crystal

color 

White to Light yellow

λmax

313nm(H2O)(lit.)

CAS DataBase Reference

16588-24-2

Safety Information

Hazard Codes 

Xi

HazardClass 

IRRITANT

HS Code 

2904990090

4-Bromo-1-chloro-2-nitrobenzene Usage And Synthesis

Uses

4-Bromo-1-chloro-2-nitrobenzene (5-Bromo-2-chloronitrobenzene) is a pharmaceutical intermediate compound used in the preparation of vismodegib, a molecular inhibitor of the Hedgehog signalling pathway approved for the treatment of metastatic and locally advanced basal cell carcinoma (BCC).

Synthesis

General procedure for the synthesis of 5-bromo-2-chloronitrobenzene from 3-nitro-4-chloroaniline: 4-chloro-3-nitroaniline (17.2 g, 0.1 mol) was dissolved in 260 mL of 48% hydrobromic acid (HBr) at 0 °C. Subsequently, an aqueous solution of sodium nitrite (NaNO2, 13.8 g, 0.2 mol) was added slowly and dropwise. The reaction mixture was stirred continuously for 1 h at 0 °C. After that, cuprous bromide (CuBr, 24 g, 0.17 mol) was added in batches and stirring was continued for 1 hour at 0°C. Upon completion of the reaction, water was added and the mixture was gradually warmed to room temperature and extracted with ethyl acetate (EtOAc). The crude product was purified by silica gel column chromatography to give the final 5-bromo-2-chloronitrobenzene (13 g, 55% yield). The structure of the product was confirmed by 1H NMR (CDCl3, 400 MHz): δ 8.03-8.02 (m, 1H), 7.66-7.63 (m, 1H), 7.45-7.42 (m, 1H).

References

[1] Patent: WO2013/117522, 2013, A1. Location in patent: Page/Page column 40
[2] Patent: US2015/18367, 2015, A1. Location in patent: Paragraph 0177; 0178
[3] Journal of the American Chemical Society, 1962, vol. 84, p. 1026 - 1032
[4] Journal of Organic Chemistry USSR (English Translation), 1967, vol. 3, p. 1795 - 1799
[5] Zhurnal Organicheskoi Khimii, 1967, vol. 3, # 10, p. 1839 - 1843

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