Dimethylformamide → 4-Cyclopropoxybenzaldehyde

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Reaction Steps

To a solution of 1-bromo-4-(cyclopropoxy)benzene (492 mg, 2.31 mmol) in tetrahydrofuran (10 ml) was added dropwise a solution of 2.66 mol/L n-butyllithium in hexane (0.955 ml, 2.54 mmol) at −78° C. under argon atmosphere, and the mixture was stirred for 2.5 hours. Then, thereto was added dropwise N,N-dimethylformamide (0.358 ml, 4.62 mmol) at the same temperature, and the mixture was stirred for 3.5 hours with slowly warming to room temperature. To the reaction solution was added saturated aqueous ammonium chloride solution, and the mixture was stirred, and then extracted with ethyl acetate three times. The organic layer was combined, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give a crude 4-(cyclopropoxy)benzaldehyde as a pale yellow liquid. The resulting compound was used in the next step without further purification. (2) A solution of the above crude product in methanol (5 ml) was cooled to 0° C., and then thereto was added sodium borohydride (175 mg, 4.62 mmol), and the mixture was stirred for 1 hour. Then, thereto was added saturated brine, and then the reaction solution was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→3:2) to give the title compound, [4-(cyclopropoxy)phenyl]methanol (216 mg, 57%, yields for 2 steps) as a white solid.

Provenance & Evidence