15969-10-5

Step 1: 4-Chloro-2-nitrophenol (1.0 eq.) was dissolved in acetic acid (0.64 M) and cooled under ice bath conditions. Subsequently, bromine (1.1 eq.) was added slowly and dropwise to the reaction system, keeping the reaction mixture stirred in an ice bath for 3 hours, during which time it was gradually warmed up to room temperature. After completion of the reaction, bromine (0.3 eq.) was added to the system and stirring was continued for 1 hour. The progress of the reaction was monitored by thin layer chromatography (TLC) to confirm that the reaction was essentially complete. Subsequently, pre-cooled deionized water was added to the reaction mixture, which immediately produced a yellow suspension. The mixture was stirred vigorously and the precipitate was collected by filtration. The resulting yellow-orange solid was washed sequentially with deionized water and heptane to obtain a yellow powdery product. The product was dried in a high vacuum drying oven for 3 days to give 2-bromo-4-chloro-6-nitrophenol in 76% yield. The product was analyzed by liquid chromatography-mass spectrometry (LC-MS) showing (m/z) [M+H]+=291.9 and retention time (Rt)=1.45 min.

[1] Journal of Organic Chemistry, 2018, vol. 83, # 14, p. 7388 - 7397
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[3] Patent: WO2013/49605, 2013, A1. Location in patent: Paragraph 0054
[4] Patent: WO2016/38582, 2016, A1. Location in patent: Paragraph 00335
[5] American Chemical Journal, 1904, vol. 32, p. 15