Synthesis
To a solution of 3-amino-4-chlorobenzoic acid (15.0 g, 88.0 mmol) in methanol (90.0 mL), thionyl chloride (13.0 mL) was added drop-wise at 0 °C. The resulting mixture was refluxed for 12h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue was diluted with water (150 mL) and extracted with ethyl acetate. The organic layer was washed with sodium bicarbonate (50 mL) and brine solution (50 mL) and dried over sodium sulfate. The organic layer was removed under a rotary evaporator to yield Methyl 3-amino-4-chlorobenzoate (15.0 g, 92.5 per cent) as an off-white solid. 1H NMR (400 MHz, CDC13) δ 3.88 (s, 3H), 4.26 (brs, 2H), 7.29 (d, J = 8.2 Hz, 1H), 7.34-7.37 (dd, J = 1.9, 8.2 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H).
References
[1] Patent: WO2011/128251, 2011, A1. Location in patent: Page/Page column 201
[2] Patent: US2011/257151, 2011, A1. Location in patent: Page/Page column 74
[3] Patent: WO2014/149164, 2014, A1. Location in patent: Paragraph 00708
[4] Journal of Medicinal Chemistry, 2009, vol. 52, # 8, p. 2465 - 2481
[5] Journal of Organic Chemistry, 2003, vol. 68, # 5, p. 2051 - 2053
