Synthesis
The general procedure for the synthesis of 4-bromo-2-hydroxymethylbenzoic acid using 5-bromophthalide as starting material was as follows: 5-bromophthaloyl (9 g, 0.042 mol) was dissolved in methanol (150 ml), 2N aqueous sodium hydroxide (100 ml) was added, and the reaction was carried out at reflux overnight. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The concentrate was diluted with water and acidified with dilute hydrochloric acid to appropriate pH. The precipitated solid precipitate was collected by filtration and the residue was washed sequentially with cold water and cold ethyl acetate and dried to give 4-bromo-2-hydroxymethylbenzoic acid (9.7 g, 100% yield) as a white solid.
References
[1] Patent: US2008/15237, 2008, A1. Location in patent: Page/Page column 33
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 16, p. 7144 - 7167
[3] Patent: WO2015/89327, 2015, A1. Location in patent: Paragraph 0375
[4] Bulletin de la Societe Chimique de France, 1954, p. 769,772
[5] Journal of the Chemical Society, 1931, p. 867,869
