877149-08-1

To a tert-butanol (21.7 mL) suspension of 4-bromo-2-methoxy-6-methylbenzaldehyde (1.25 g, 5.45 mmol) was sequentially added an aqueous (11 mL) solution of sodium chlorite (0.98 g, 10.9 mmol) and sodium dihydrogen phosphate (4.25 g, 27.3 mmol). Subsequently, 2-methyl-2-butene (4.63 mL, 43.7 mmol) was added to this mixed solution. The reaction mixture was stirred at room temperature for 30 minutes until the reaction was complete. Upon completion of the reaction, the solvent was removed by evaporation and the residue was diluted with water and acidified with 1 M hydrochloric acid to pH=1. The acidified solution was extracted with methyl tert-butyl ether (3 x 40 mL). The organic layers were combined, back-extracted with 1 M sodium hydroxide solution, and acidified with 6 M hydrochloric acid to pH=1. The acidified aqueous phase was extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, washed with brine (40 mL), dried over anhydrous sodium sulfate and concentrated to give 4-bromo-2-methoxy-6-methylbenzoic acid (1.2 g, 4.89 mmol, 90% yield).

[1] Patent: WO2013/156155, 2013, A1. Location in patent: Page/Page column 135; 136
[2] Patent: US2013/281452, 2013, A1. Location in patent: Paragraph 0677
[3] Patent: WO2011/123536, 2011, A1. Location in patent: Page/Page column 75-76
[4] Patent: WO2012/21712, 2012, A1. Location in patent: Page/Page column 63-64
[5] Journal of Medicinal Chemistry, 2013, vol. 56, # 20, p. 8112 - 8138