29415-97-2

A reactant used in the preparation of selective inhibitors. In unsymmetrical Ullman reaction between methyl 5bromovanillate (II) and methyl 3-bromo-4-hydroxybenzoate (III) yielded all the three possible dicarbomethoxy-dibenzo-pdioxms which were separated by repeated chromatography over silica gel. A phosphorus- and bromine-containing bifunctional monomer has been prepared from bis(chloromethyl)methylphosphine oxide and the sodium salt of methyl 3-bromo-4-hydroxybenzoate.

The general procedure for the synthesis of methyl 3-bromo-4-hydroxybenzoate from methanol and 3-bromo-4-hydroxybenzoic acid is as follows: 1. Preparation of intermediate T3.1 (methyl 3-bromo-4-hydroxybenzoate): - Under stirring conditions, 3-bromo-4-hydroxybenzoic acid (50.0 g, 231 mmol) was dissolved in methanol (300 mL). - To the above solution was slowly added cold sulfuric acid solution (2.50 mL, 47 mmol). - The reaction mixture was heated to 80 °C and the progress of the reaction was monitored by thin layer chromatography (TLC). - After 16.5 h of reaction, the solvent was removed by distillation under reduced pressure. - The reaction mixture was diluted with ethyl acetate (EtOAc). - The organic phase was sequentially washed twice with saturated aqueous sodium bicarbonate (NaHCO3), once with brine and then dried with anhydrous sodium sulfate. - After filtration, the organic solvent was removed by distillation under reduced pressure to give the intermediate T3.1 as a white solid in 100% yield, which can be used in the next reaction without further purification.

[1] Patent: WO2010/45258, 2010, A2. Location in patent: Page/Page column 119
[2] Patent: WO2009/111056, 2009, A1. Location in patent: Page/Page column 103; 141
[3] Patent: WO2017/36404, 2017, A1. Location in patent: Paragraph 57; 58
[4] Patent: EP2380890, 2011, A1. Location in patent: Page/Page column 35
[5] Macromolecules, 2003, vol. 36, # 12, p. 4328 - 4336