Example 16-1 Preparation of 3-hydroxy-5-methoxybenzaldehyde
60% sodium hydride (2.77 g, 69.3 mmol) was slowly added to ethanol thiol (7 ml) followed by N,N-dimethylformamide (50 ml) at 0°C. The reaction mixture was stirred at 0°C for 30 min and then heated to reflux for 1 hr. After cooling to room temperature, a solution of N,N-dimethylformamide (90 ml) of 3,5-dimethoxybenzaldehyde (3.84 g, 23.1 mmol) was added and heated to reflux for 1 hour again. After completion of the reaction, the mixture was cooled to room temperature and saturated aqueous sodium chloride solution (700 ml), 26% aqueous formaldehyde solution (70 ml) and acetic acid (130 ml) were added sequentially. The mixture was stirred and extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated aqueous sodium chloride solution and dried with anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=2:1) to afford the target product 3-hydroxy-5-methoxybenzaldehyde (2.68 g, 17.6% yield).
1H NMR (CDCl3,400MHz) δ 9.88 (s, 1H), 7.00 (m, 1H), 6.96 (m, 1H), 6.68 (t, 1H, J=2.3Hz), 3.84 (s, 3H).
