Synthesis
General procedure for the synthesis of (2-amino-4-fluorophenyl)-carbamic acid-1,1-dimethylethyl ester from tert-butyl (4-fluoro-2-nitrophenyl)carbamate: To a solution of tetrahydrofuran (THF, 30 mL) of tert-butyl 4-fluoro-2-nitrophenylcarbamate (0.34 g) was added a pre-mixed aqueous solution of sodium bisulphite (2 g) and sodium bicarbonate (1 g) ( 50mL). To promote dissolution of the mixture, additional methanol (MeOH, 10 mL) was added, followed by stirring for 30 min at room temperature. Upon completion of the reaction, sodium chloride was added to saturate the solution. The reaction mixture was extracted with ethyl acetate (EtOAc, 2 x 30 mL). The organic phases were combined, dried over anhydrous sodium sulfate and filtered, and concentrated under reduced pressure to afford (2-amino-4-fluorophenyl)-carbamic acid-1,1-dimethylethyl ester (quantitative yield), and the product could be used in the subsequent reaction without further purification. The product was characterized by 1H-NMR (300 MHz, CDCl3): δ 7.5 (dd, 1H), 6.6 (dd, 1H), 6.5 (m, 1H), 6.4 (br s, 1H), 4.7 (br s, 2H), 1.5 (s, 9H) ppm; mass spectrometry analysis showed MH+ = 227 (minor peaks), 127 (-BOC fragment), 171 (-tBu fragment).
References
[1] Patent: US2008/85898, 2008, A1. Location in patent: Page/Page column 15
[2] Patent: US2008/119496, 2008, A1. Location in patent: Page/Page column 26
[3] Patent: WO2008/60301, 2008, A1. Location in patent: Page/Page column 63-64
[4] Patent: WO2009/48474, 2009, A1. Location in patent: Page/Page column 28
[5] Patent: CN107879975, 2018, A. Location in patent: Paragraph 0164; 0166
