Synthesis
Step 1: Suspend 5-methylsalicylaldehyde (2-hydroxy-5-methylbenzaldehyde, CAS No. 613-84-3) in a solvent mixture of 5 mL dichloromethane and 5 mL water. 1.47 mL (4.4 mmol, 3 eq.) of 1 N sodium hydroxide solution and 1.52 g (2.94 mmol, 2 eq.) of 50% aqueous tetrabutylammonium hydroxide were added sequentially, followed by iodomethane (457 μL, 5 eq.). The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was extracted with dichloromethane three times, the organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel fast column chromatography (eluent: cyclohexane/ethyl acetate, 9/1, v/v) to afford 215 mg (97% yield) of the target compound 2-methoxy-5-methylbenzaldehyde.
References
[1] Canadian Journal of Chemistry, 2012, vol. 90, # 11, p. 965 - 974
[2] Journal of Medicinal Chemistry, 2002, vol. 45, # 19, p. 4188 - 4201
[3] Patent: WO2010/66847, 2010, A1. Location in patent: Page/Page column 70
[4] Indian Journal of Chemistry - Section B Organic Chemistry Including Medicinal Chemistry, 1990, vol. 29, # 9, p. 876 - 878
[5] Beilstein Journal of Organic Chemistry, 2018, vol. 14, p. 734 - 746
