3-hydroxy-4-(3-methoxypropoxy)benzaldehyde

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium carbonate (14.7 g, 106 mmol) and benzyl chloride (12.2 mL, 106 mmol) were added to a solution of 3-hydroxy-4-(3-methoxypropoxy)benzaldehyde described in Production Example 32-1 (17.2 g, 81.7 mmol) in ethanol (200 mL) under nitrogen atmosphere at room temperature, and the mixture was stirred under a thermal condition of 90° C. for 2 hours. The reaction liquid was cooled to 0° C., and the mixture was diluted with 2 M hydrochloric acid, ethyl acetate, and water. The organic layer was washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. The drying agent was separated by filtration and then the filtrate was concentrated under vacuum. The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=4:1-3:7) to obtain the title compound (19.8 g, 81%). The reaction liquid was cooled to 0° C. The organic layer was washed with a saturated saline solution dried over anhydrous magnesium sulfate The drying agent was separated by filtration the filtrate was concentrated under vacuum The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=4:1-3:7)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 1-bromo-3-methoxypropane (24.0 g, 157 mmol) was added to a solution of commercially available 3,4-dihydroxybenzaldehyde (21.7 g, 157 mmol) and sodium carbonate (25.0 g, 236 mmol) in N,N-dimethylformamide (50 mL) under nitrogen atmosphere at room temperature. The reaction liquid was stirred at room temperature for 3 days and 4 hours. 2 M hydrochloric acid, ethyl acetate, and water were added to the reaction liquid at 0° C. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed serially with water and a saturated saline solution and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration and the filtrate was concentrated under vacuum. The insoluble matters were separated by filtration with dichloromethane and the filtrate was concentrated under vacuum. The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=17:3-1:1) to obtain the title compound (17.2 g, 52%). The reaction liquid The aqueous layer was extracted with ethyl acetate The combined organic layer was washed serially with water a saturated saline solution and then dried over anhydrous sodium sulfate The drying agent was separated by filtration the filtrate was concentrated under vacuum The insoluble matters were separated by filtration with dichloromethane the filtrate was concentrated under vacuum The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=17:3-1:1)