Synthesis
Step 3: Synthesis of 5-chloro-2-ethylaniline
A methanol (50 mL) solution of hydrazine hydrate (6.95 mL, 134.7 mmol) was slowly added dropwise to a methanol (120 mL) solution of 4-chloro-1-ethyl-2-nitrobenzene (6.25 g, 33.7 mmol). Ferric (III) chloride (547 mg, 3.4 mmol) and activated carbon (547 mg) were added as catalysts to the reaction system. The reaction mixture was stirred under reflux conditions for 13 hours. After completion of the reaction, the solid catalyst was removed by diatomaceous earth filtration and the filtrate was concentrated. The resulting crude product was purified by fast chromatography (eluent: hexane/ethyl acetate = 9:1) to afford the light pink oily target compound 5-chloro-2-ethylaniline (5.09 g, 97% yield).
1H NMR (400 MHz, DMSO-d6) δ ppm: 1.09 (t, J = 7.51 Hz, 3H), 2.39 (q, J = 7.49 Hz, 2H), 5.13 (s, 2H), 6.47 (dd, J = 8.06, 2.20 Hz, 1H), 6.62 (d, J = 2.20 Hz, 1H), 6.89 (d, J = 8.06 Hz, 1H). J = 8.06 Hz, 1H).
References
[1] Patent: WO2016/106331, 2016, A1. Location in patent: Paragraph 0222
[2] Patent: WO2012/139930, 2012, A1. Location in patent: Page/Page column 72
[3] Patent: WO2012/143248, 2012, A1. Location in patent: Page/Page column 24
[4] Patent: WO2014/19908, 2014, A2. Location in patent: Page/Page column 33
[5] Patent: US2014/51708, 2014, A1. Location in patent: Paragraph 0722; 0723
