Uses
2-Hydroxy-3-methoxy-3,3-diphenylpropanoic Acid is used as a reactant in the preparation of mixed endothelin A and endothelin B selective receptor antagonist (dimethylpyrimidinyloxy)diphenylpropionic acids.
Synthesis
General procedure for the synthesis of 2-hydroxy-3-methoxy-3,3-diphenylmethylpropionic acid from methyl 2-hydroxy-3-methoxy-3,3-diphenylpropionate: 500 g (1.75 mol) of (RS)-2-hydroxy-3-methoxy-3,3-diphenylmethylpropionate was suspended in 1,000 mL of water with stirring and 950 mL (1.90 mol) of 2 mol/L sodium hydroxide solution. The reaction mixture was stirred at 100°C for 1 hour. Upon completion of the reaction, the solution was cooled to room temperature and 1,500 mL of tert-butyl methyl ether was added followed by 700 mL of 10% hydrochloric acid and stirred for 20 minutes to dissolve the precipitated solids. After performing a liquid-liquid separation, the organic layer was washed with 1,000 mL of water. To the organic layer, 1,200 mL of heptane was added and the solvent was removed by distillation under reduced pressure at 40 °C and 200 mmHg pressure to induce precipitation of crystals. Another 1,000 mL of heptane was added and the mixture was stirred at 0 °C for 1 hour. The crystals were collected by filtration and dried under reduced pressure at 40 °C for 7 h to give 431 g (91% yield) of (RS)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid.
References
[1] Patent: JP2017/128528, 2017, A. Location in patent: Paragraph 0005; 0040
[2] Patent: WO2012/17441, 2012, A1. Location in patent: Page/Page column 11
[3] Patent: WO2010/70658, 2010, A2. Location in patent: Page/Page column 18-19
[4] Patent: US2011/263854, 2011, A1. Location in patent: Page/Page column 8
[5] Organic Process Research and Development, 2001, vol. 5, # 1, p. 16 - 22
