Synthesis
(Trimethylmethylsilyl) diazomethane (2.0 M ethyl ether solution, 18.0 mL, 36.0 mmol) was added slowly and dropwise to a 10% methanolic tetrahydrofuran solution (100 mL) of 4-methoxyanthranilic acid (5.0 g, 30.0 mmol) at 0 °C. The reaction mixture was kept stirred at room temperature for 16 h. The reaction was subsequently terminated by addition of glacial acetic acid (0.1 mL). The reaction mixture was concentrated and the residue was partitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (250 mL). The organic layer was separated and washed sequentially with water (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford methyl 2-amino-4-methoxybenzoate as an oil (5.4 g, quantitative). Mass spectrometry (EI) analysis showed a molecular ion peak (MH+) of 182 for C9H11NO3.
References
[1] Patent: WO2010/135524, 2010, A1. Location in patent: Page/Page column 219
[2] Patent: WO2013/25958, 2013, A1. Location in patent: Page/Page column 69; 70
[3] Patent: WO2014/43446, 2014, A1. Location in patent: Page/Page column 31
[4] Patent: EP2744501, 2016, B1. Location in patent: Paragraph 0204; 0205
[5] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3170 - 3181
