Synthesis
To a stirred solution of methyl 4-fluoro-3-nitrobenzoate (CAS 329-59-9, 5.00 g, 25.1 mmol) in N,N-dimethylformamide (DMF, 50 mL) was sequentially added methylamine hydrochloride (2.00 g, 29.6 mmol) and potassium carbonate (4.50 g, 32.6 mmol). The reaction mixture was stirred at room temperature for 18 hours under nitrogen protection. Upon completion of the reaction, the crude product was concentrated under reduced pressure and the residue was extracted by partitioning with ethyl acetate (EtOAc, 350 mL) and aqueous 1N hydrochloric acid (250 mL). The organic layer was washed sequentially with aqueous 1N hydrochloric acid (150 mL) and saturated aqueous sodium chloride (100 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the yellow powdery product methyl 4-(methylamino)-3-nitrobenzoate (EV-AR3152-001, 5.30 g, quantitative yield).Results of LC-MS (Method D) analysis: retention time 1.07 min, m/z = 211 ([M+H]+).
References
[1] Patent: WO2017/100594, 2017, A1. Location in patent: Paragraph 00130
[2] Patent: WO2018/22897, 2018, A1. Location in patent: Paragraph 00126; 00127; 00128
[3] Patent: WO2017/147102, 2017, A1. Location in patent: Paragraph 00124-00125
