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0 °C

To a mixture of ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (0.29 g, 1.34 mmol), {4-[(2-phenyl-1H-indol-1-yl)methyl]phenyl}methanol (0.38 g, 1.22 mmol), tributylphosphine (0.46 mL, 1.83 mmol) and tetrahydrofuran (7.6 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.46 g, 1.83 mmol) with stirring at 0° C., and the mixture was stirred at room temperature for 18 hr. Diethyl ether was added to the reaction mixture. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1) to give a colorless oil. Then, a mixture of the obtained oil, 1 N aqueous sodium hydroxide solution (2.5 mL), methanol (5.0 mL) and tetrahydrofuran (10.0 mL) was stirred at room temperature for 14 hr. The reaction mixture was diluted with ethyl acetate, and the mixture washed with 1 N hydrochloric acid, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=1/2) to give the title compound (0.46 g, yield 79%) as colorless crystals. MS (APCI−): 478 (M−H), 1H NMR (CDCl3) δ: 2.64 (2H, t, J=7.8 Hz), 2.91 (2H, t, J=7.8 Hz), 4.96 (2H, s), 5.38 (2H, s), 6.61-6.70 (3H, m), 7.01-7.20 (6H, m), 7.32 (2H, d, J=8.1 Hz), 7.34-7.47 (5H, m), 7.67 (1H, m).

1. stirringthe mixture was stirred at room temperature for 18 hr
2. filtrationThe insoluble material was filtered off
3. concentrationthe filtrate was concentrated under reduced pressure
4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1)
5. customto give a colorless oil
6. stirringwas stirred at room temperature for 14 hr
7. washthe mixture washed with 1 N hydrochloric acid, water and saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=1/2)