Uses
2,4-Dibromobenzoic Acid Methyl Ester is used in the preparation of compounds with immunosuppressive inhibitory activity and antitumor activity.
Uses
2,4-Dibromobenzoic Acid Methyl Ester is sued in the preparation of compounds with immunosuppressive inhibitory activity and antitumor activity.
Synthesis
Step 1: In a 2L round-bottomed flask, 2,4-dibromobenzoic acid (250 g, 0.90 mol) was dissolved in methanol (2L) and concentrated sulfuric acid (18.4 g, 0.19 mol) was added. The reaction mixture was heated to reflux overnight and subsequently cooled to room temperature. The resulting precipitate was collected by filtration, washed with cold methanol and dried under vacuum to give 213.6 g of methyl 2,4-dibromobenzoate, the product was a yellow solid. Step 2: In another 2L round-bottomed flask, methyl 2,4-dibromobenzoate (200.7 g, 0.69 mol) was dissolved in 1L of anhydrous N,N-dimethylformamide (DMF). Copper cyanide (CuCN, 123.8 g, 1.38 mol) and sodium iodide (NaI, 22.8 g, 0.15 mol) were added sequentially. The reaction mixture was stirred at 160 °C overnight under nitrogen protection. Upon completion of the reaction, extraction was carried out with ethyl acetate (500 mL x 3), and the combined organic phases were washed with 500 mL of water. Purification by silica gel column chromatography (eluent: petroleum ether/ethyl acetate=5/1) afforded 93.5 g of methyl 2,4-dicyanobenzoate, the product was a brown solid with 72.8% yield.
References
[1] Patent: EP3048103, 2016, A1. Location in patent: Paragraph 0077; 0078
[2] Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 2490 - 2494
[3] Chemistry - A European Journal, 2010, vol. 16, # 6, p. 1780 - 1784
[4] Asian Journal of Chemistry, 2014, vol. 26, # 19, p. 6655 - 6657
