Synthesis
Step-1: 2-Amino-4-fluorobenzoic acid (50 g, 322.6 mmol) was dissolved in 700 mL of N,N-dimethylformamide (DMF) followed by addition of N-chlorosuccinimide (41 g, 305.5 mmol) in batches. The reaction mixture was heated at 50 °C with stirring for 5 hours. Upon completion of the reaction, the mixture was cooled to room temperature and slowly poured into ice water to precipitate a solid. The solid was collected by filtration, dissolved in ethyl acetate (EtOAc) and washed with saturated sodium chloride solution (300 mL). The aqueous layer was back-extracted with ethyl acetate (3 x 200 mL). The organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give the product 2-amino-5-chloro-4-fluorobenzoic acid (42 g, 69% yield) as a brown solid.
References
[1] Patent: WO2016/171755, 2016, A1. Location in patent: Paragraph 0101
[2] Patent: US2016/311818, 2016, A1. Location in patent: Paragraph 0465; 0466
[3] Patent: US2010/120741, 2010, A1. Location in patent: Page/Page column 122
[4] Patent: WO2011/112731, 2011, A2. Location in patent: Page/Page column 251
