Synthesis
At 25 °C and under nitrogen protection, 2-fluoro-4-hydroxybenzaldehyde (1.0 g, 7.1 mmol) and potassium carbonate (2.0 g, 14 mmol) were dissolved in N,N-dimethylformamide (10 mL), followed by the addition of ethyl iodide (1.1 g, 7.1 mmol). The reaction mixture was stirred at 60 °C for 10 hours. After completion of the reaction, the mixture was concentrated in vacuum, diluted with ethyl acetate (200 mL), washed sequentially with saturated sodium bicarbonate solution (3 x 50 mL) and brine (3 x 50 mL), and the organic phase was dried with anhydrous sodium sulfate. After drying, the organic phase was concentrated in vacuum to afford the target product 4-ethoxy-2-fluorobenzaldehyde (1.0 g, 83% yield) as a red solid.1H-NMR (CD3OD, 400 MHz) data were as follows: δ 10.09 (s, 1H), 7.76-7.67 (m, 1H), 6.83-6.74 (m, 2H), 4.11 (t, J = 6.8 Hz, 2H), 1.40 (t, J = 7.0 Hz, 3H).
References
[1] Patent: WO2016/100184, 2016, A1. Location in patent: Paragraph 00537-00538
[2] Patent: WO2016/201096, 2016, A1. Location in patent: Paragraph 00335
