Synthesis
Step 1: Preparation of 5-chloro-2-methoxybenzaldehyde
5-Chloro-2-hydroxybenzaldehyde (20 g, 128 mmol) was dissolved in N,N-dimethylformamide (DMF, 70 mL) and the solution was cooled to 5-10 °C. Sodium hydride (7.69 g, 192 mmol) was added to the solution in small portions over 20 min. Subsequently, iodomethane (23.8 mL, 384 mmol) was added dropwise while keeping the temperature of the reaction mixture below 15 °C. After addition, the reaction mixture was stirred at room temperature for 2 hours. Upon completion of the reaction, the mixture was poured into pre-cooled saturated ammonium chloride solution (250 mL) and a white precipitate precipitated. The precipitate was collected by filtration and dried under vacuum. The resulting solid was ground with a solvent mixture of pentane and ether (4:1, 100 mL) to afford 18 g (82.58% yield) of the target product, 5-chloro-2-methoxybenzaldehyde, as a white solid.LC-MS analysis showed m/z = 170.1 ([M+H]+).
References
[1] Chemical Communications, 2011, vol. 47, # 9, p. 2679 - 2681
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 12, p. 5019 - 5032
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 12, p. 2768 - 2776
[4] Patent: WO2014/151472, 2014, A1. Location in patent: Paragraph 00392-00393
[5] Patent: WO2016/40315, 2016, A1. Location in patent: Paragraph 00435; 00436
