反应详情

To a solution of 2-[4-(ethylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (1.30 g) in N,N-dimethylformamide (20 mL) were added N-methoxymethanamine hydrochloride (582 mg), triethylamine (1.67 mL), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (840 mg) and 1-hydroxybenzotriazole (670 mg), and the mixture was stirred at room temperature for 3 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-0:100, volume ratio) to give a colorless oil. A solution of the obtained oil in tetrahydrofuran (40 mL) was purged with nitrogen, and a 1.0M vinylmagnesium bromide tetrahydrofuran solution (12 mL) was added under ice-cooling. The reaction solution was warmed to room temperature, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was added to 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-80:20, volume ratio) to give the title compound (1.20 g, yield 90%) as a colorless oil. MS: 337 (MH+).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed successively with water and saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-0:100, volume ratio)
6. customto give a colorless oil
7. customA solution of the obtained oil in tetrahydrofuran (40 mL) was purged with nitrogen
8. additiona 1.0M vinylmagnesium bromide tetrahydrofuran solution (12 mL) was added under ice-
9. temperaturecooling
10. temperatureThe reaction solution was warmed to room temperature
11. stirringthe mixture was stirred at room temperature for 1 hr
12. additionThe reaction mixture was added to 1M hydrochloric acid
13. extractionthe mixture was extracted with ethyl acetate
14. washThe extract was washed successively with water and saturated brine
15. dry with materialdried over anhydrous magnesium sulfate
16. concentrationconcentrated under reduced pressure
17. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-80:20, volume ratio)