Synthesis
The general procedure for the synthesis of 4-benzyloxy-3-ethoxybenzaldehyde from ethyl vanillin and benzyl bromide was as follows: to a solution of N,N-dimethylformamide (5 mL) of 3-ethoxy-4-hydroxybenzaldehyde (830 mg, 5 mmol) was slowly added K2CO3 (20 mg), followed by the dropwise addition of benzyl bromide (6 mmol) at a temperature of less than 40 °C. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the mixture was poured into ice water (10 mL) and extracted with diethyl ether. The organic phase was washed sequentially with water and sodium hydroxide solution, dried and concentrated to give 4-benzyloxy-3-ethoxybenzaldehyde (18) (1.1 g, 85% yield). Referring to the synthesis of compounds 11-16, compound 18 was reacted with locustine to produce 14-(4-(benzyloxy)-3-ethoxybenzylidene)locustine (20) (120 mg, 30% yield).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 5, p. 1495 - 1497
[2] Patent: EP1577290, 2005, A1. Location in patent: Page/Page column 95
[3] Patent: EP1640360, 2006, A1. Location in patent: Page/Page column 59
