Synthesis
2-Hydroxy-4-bromobenzoic acid (5.0 g, 23.1 mmol) was dissolved in 20 mL of anhydrous methanol and 1.7 mL of concentrated sulfuric acid was added slowly. The reaction mixture was heated and refluxed under stirring for 24 hours. Upon completion of the reaction, the reaction solution was poured into ice water and concentrated by rotary evaporator to remove methanol. Subsequently, extraction was carried out with ethyl acetate (EA) and the organic phase was washed with saturated sodium bicarbonate (NaHCO3) solution and dried over anhydrous sodium sulfate. Finally, the organic phase was concentrated to afford methyl 2-hydroxy-4-bromobenzoate (5.31 g) as a reddish brown solid, and the product was used directly in the next reaction without further purification.
References
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3228 - 3241
[2] Patent: US2016/221997, 2016, A1. Location in patent: Paragraph 0245; 0246; 0247
[3] Patent: WO2016/115282, 2016, A1. Location in patent: Page/Page column 76
[4] Patent: WO2015/163485, 2015, A1. Location in patent: Paragraph 0372
[5] Tetrahedron Letters, 2016, vol. 57, # 48, p. 5301 - 5303
