Chemical Properties
clear yellow liquid
Uses
It is a useful synthetic intermediate. It was used in the synthesis of irreversible inhibitors of EGFR and HER-2 tyrosine kinases with enhanced antitumor activities.
Preparation
ethyl or methyl crotonate is treated with N-Bromosuccinimide/CCl4 and Dibenzoyl Peroxide.
Synthesis
General procedure for the synthesis of methyl 4-bromobut-2-enoate from methanol and (E)-4-bromobut-2-enoic acid: (E)-4-bromobut-2-enoic acid (1.525 g, 9.24 mmol) and anhydrous methanol (10 ml) were added to a 50 ml three-necked flask, and stirred at 0 °C until complete dissolution. Subsequently, sulfoxide chloride (5.49 g, 46.19 mmol, 5 ml) was added slowly dropwise, taking care to control the rate of titration to avoid violent outgassing. After dropwise addition, the reaction mixture was gradually warmed up to room temperature and the reaction was continued with stirring for 15 h. The reaction progress was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was concentrated to dryness under reduced pressure. The residue was extracted with ethyl acetate and water to separate the organic and aqueous phases. The organic phase was collected and dried with anhydrous sodium sulfate. The dried organic phase was concentrated under reduced pressure to remove the solvent to give the crude product. The crude product was purified by column chromatography with petroleum ether:ethyl acetate=8:1 (v/v) as eluent, resulting in 1.54 g of a red oily liquid of methyl 4-bromobut-2-enoate (compound 26) in 93.1% yield.
storage
handle under nitrogen and in a fume hood. Store refrigerated and tightly closed.
References
[1] Patent: CN107556289, 2018, A. Location in patent: Paragraph 0112; 0117; 0118; 0119
[2] Tetrahedron Asymmetry, 2009, vol. 20, # 10, p. 1164 - 1167
