90064-48-5

A mixture was prepared from 1-chloro-2,5-dimethoxybenzene (compound 4, 1.0 g, 5.79 mmol) and hexamethylenetetramine (893 mg, 6.37 mmol) in THF. To the mixture 2,2,2-trifluoroacetic acid (TFA, 12.89 mg, 113 mmol) was slowly added. The reaction mixture was heated to reflux for 2 hours. After completion of the reaction, the hot reaction solution was carefully poured into ice and the pH was adjusted with NaHCO3 powder to 7. The mixture was extracted with ethyl acetate and the organic phases were combined, washed with brine and dried over anhydrous Na2SO4. The organic phase was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography to afford 4-chloro-2,5-dimethoxybenzaldehyde (compound 5, 543 mg, white solid) in 47% yield.

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