General procedure for the synthesis of methyl 4-amino-3,5-dichlorobenzoate from methanol and 4-amino-3,5-dichlorobenzoic acid: Thionyl chloride (2.14 g, 0.018 mol) was slowly added dropwise to methanol (10 mL) via a syringe under the condition of -3 to -4 °C. The reaction temperature was controlled not to exceed -1.1 °C during the dropwise addition, and the time of the dropwise addition was about 35 min. After the dropwise addition, the reaction mixture was stirred at 0 °C or lower for 1 hour. Subsequently, 4-amino-3,5-dichlorobenzoic acid (0.75 g, 3.6 mmol) [ACROS Organics] was added in a single addition. The reaction mixture was stirred at room temperature for about 3 days until the reaction was complete. After completion of the reaction, the homogeneous reaction mixture was concentrated under vacuum. Water (6 mL) was added to the concentrated residue and sodium bicarbonate (0.36 g, 4.3 mmol) was added all at once and stirred for 30 minutes at room temperature. The mixture was extracted several times with ethyl acetate. All organic phases were combined, dried with anhydrous sodium sulfate, filtered, and concentrated under vacuum to afford methyl 4-amino-3,5-dichlorobenzoate 0.79 g (quantitative yield) as a brown solid product. Mass spectrum (MS): m/z 220 (MH+). Nuclear magnetic resonance hydrogen spectrum (1H NMR, 500 MHz, DMSO-d6): δ 3.780 (s, 3H), 6.407 (br s, 2H), 7.731 (s, 2H).
