Synthesis
Potassium carbonate (K2CO3, 32.0 g, 0.232 mol) and iodomethane (24.0 mL, 0.384 mol) were sequentially added to an N,N-dimethylformamide (DMF, 150 mL) solution of 3,5-dichlorosalicylic acid (17, 20.0 g, 0.097 mol) in an ice-water bath. The reaction mixture was stirred at room temperature for 24 hours. After completion of the reaction, the solvent was evaporated to dryness by rotary evaporator. The residue was subjected to liquid-liquid partitioning with ether and water. The organic phase was washed sequentially with 1N sodium hydroxide (NaOH) solution and saturated brine, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated to afford the target product methyl 3,5-dichloro-2-methoxybenzoate (18, 21.6 g, 95% yield) as a white solid. The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 2.7 Hz, 1H), 7.54 (d, J = 2.7 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H).
References
[1] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 129 - 137
[2] Patent: WO2017/11725, 2017, A1. Location in patent: Paragraph 0076
[3] Medicinal Chemistry Research, 1995, vol. 5, # 2/3, p. 150 - 173
