反应详情

To a solution of ethyl 5-bromo-2-ethylthiophene-3-carboxylate (5.00 g) synthesized in Example 69 (4) in tetrahydrofuran (50 mL) was added dropwise 1.0M isopropylmagnesium bromide-tetrahydrofuran solution (22.8 mL) at −45° C., and the mixture was stirred for 1 hr under an argon atmosphere. Tetrahydro-4H-pyran-4-one (5.26 mL) was added dropwise, and the mixture was stirred at −45° C. for 1 hr, and then at room temperature for 2 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, tetrahydrofuran was evaporated using evaporator, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:3, volume ratio) to give a colorless oil. To a solution of the obtained oil in trifluoroacetic acid (25 mL) was added triethylsilane (2.86 mL), and the mixture was stirred at room temperature for 1.5 hr, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio) to give the title compound (1.35 g, 26%) as a colorless oil.

1. stirringthe mixture was stirred at −45° C. for 1 hr
2. waitat room temperature for 2 hr
3. customto quench
4. customthe reaction, tetrahydrofuran
5. customwas evaporated
6. customevaporator
7. extractionthe mixture was extracted with ethyl acetate
8. washThe extract was washed with saturated brine
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:3, volume ratio)
12. customto give a colorless oil
13. stirringthe mixture was stirred at room temperature for 1.5 hr
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio)