Ethyl Acetate → 2,4-Dimethoxy-5-pyrrolidin-1-ylbenzaldehyde

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Reaction Steps

Ex-38B: To a solution of 1-pyrrolidin-1-yl-2,4-dimethoxybenzene (Ex-38A, 1.82 g, 8.78 mmol) and α,α-dichloromethyl methyl ether (1.6 mL, 17.6 mmol) in dichloromethane (50 mL) was added titanium tetrachloride (1.0 M in dichloromethane, 26.3 mL, 26.3 mmol) dropwise at 0° C. The solution was allowed to stir for 16 h at ambient temperature and poured into ice/water. The aqueous solution was extracted with dichloromethane. The combined dichloromethane was washed with saturated sodium bicarbonate, brine, dried over sodium sulfate and concentrated to give a crude product (0.67 g). The aqueous solution was further treated with solid sodium hydroxide to pH 8. The suspension was mixed with ethyl acetate. The insoluble solid was removed by filtering through a pad of Celite. The filtrate was then partitioned. The aqueous solution was further extracted with ethyl acetate. The combined ethyl acetate was washed with saturated sodium bicarbonate, brine, dried over sodium sulfate and concentrated. The combined crude product (1.71 g) was purified by flash chromatography. Elution with ethyl acetate and hexane (1:1, v/v) gave 2,4-dimethoxy-5-pyrrolidin-1-yl-benzaldehyde as a brown oil (1.03 g, 50%): 1H-NMR (300 MHz, CDCl3) δ 10.25 (s, 1H), 7.26 (s, 3H), 6.44 (s, 1H), 3.93 (s, 3H), 3.89 (s, 3H), 3.20–3.16 (m, 4H), 1.93–1.89 (m, 4H). MS m/z: 235 (M+), 100%.

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