4-methoxy-3-(2-phenylethoxy)benzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 4-Methoxy-3-(2-phenylethoxy)benzaldehyde (51.26 g), dimethyl malonate (26.43 g), piperazine (1.70 g) and acetic acid (1.20 g) were refluxed by heating in 300 ml of benzene under azeotropic dehydration conditions for 8 hours. After the reaction solution was cooled to room temperature, it was washed with water, 1 N hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of NaCl in consecutive order and dried over anhydrous magnesium sulfate. The drying agent was separated by filtration and the filtrate was concentrated under reduced pressure. The residue was recrystallized from isopropyl ether-dichloromethane to obtain 67.15 g of methyl 3-[4-methoxy-3-(2-phenylethoxy)phenyl]-2-methoxycarbonylacrylate. it was washed with water, 1 N hydrochloric acid a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of NaCl in consecutive order and dried over anhydrous magnesium sulfate The drying agent was separated by filtration the filtrate was concentrated under reduced pressure The residue was recrystallized from isopropyl ether-dichloromethane

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

Procedure: A mixture of 4-methoxy-3-(2-phenylethoxy)benzaldehyde (5.09 g), triethyl 2-phosphonobutyrate (10.76 g) and an aqueous solution of 6 M potassium carbonate (8.3 ml) was heated to 150° C. (oil bath temperature) and stirred vigorously for 8 hours. After the reaction mixture was cooled to room temperature, it was extracted with toluene. The toluene extract was washed with an aqueous solution of 0.5 N sodium hydroxide and a saturated aqueous solution of NaCl in consecutive order and dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=25:1) to obtain 4.08 g of ethyl 3-[4-methoxy-3-(2-phenylethoxy)phenyl]-2-ethylacrylate as a mixture of E- and Z-isomers (E-isomer:Z-isomer=5. 7:1). it was extracted with toluene The toluene extract was washed with an aqueous solution of 0.5 N sodium hydroxide a saturated aqueous solution of NaCl in consecutive order and dried over anhydrous magnesium sulfate The drying agent was separated by filtration the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=25:1)

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

Procedure: To a suspension of 60% sodium hydride (oily)(0.847 mg) in 25 ml of 1,2-dimethoxyethane, 4.20 ml of triethyl phosphonoacetate was added dropwise over 10 minutes and stirred at room temperature for 1 hour. To this reaction solution, 2.65 ml of pentyl bromide was added, and then refluxed by heating for 3 hours under stirring. Thereafter, the reaction solution was cooled to room temperature and 0.857 mg of 60% sodium hydride (oily) was added thereto. After stirring at room temperature for 30 minutes, 5.15 g of 4-methoxy-3-(2-phenylethoxy)-benzaldehyde was added and refluxed by heating for 2 hours under stirring. Then, the reaction solution was cooled to room temperature, and ethyl acetate and water was added thereto to separate the solution into layers. The organic layer separated was washed with water, an aqueous solution of saturated sodium hydrogencarbonate and a saturated aqueous solution of NaCl in consecutive order and dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and then the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=30:1) to thereby obtain 5.39 g of ethyl 3-[4-methoxy-3-(2-phenylethoxy)phenyl]-2-pentylacrylate as a mixture of E- and Z-isomers (E-isomer:Z-isomer=7.0:1). was added dropwise over 10 minutes refluxed by heating for 3 hours under stirring Thereafter, the reaction solution was cooled to room temperature After stirring at room temperature for 30 minutes refluxed by heating for 2 hours under stirring Then, the reaction solution was cooled to room temperature to separate the solution into layers The organic layer separated was washed with water an aqueous solution of saturated sodium hydrogencarbonate and a saturated aqueous solution of NaCl in consecutive order and dried over anhydrous magnesium sulfate The drying agent was separated by filtration the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=30:1)