反应详情

(3R,5S)-1-(tert-Butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (0.3 g) and 4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one (0.09 g) were dissolved in DMA (3.0 ml), toluenesulfonyl chloride (0.13 g), DMAP (0.014 g) and potassium carbonate (0.1 g) were added with stirring under ice-cooling, and the mixture was stirred for 6 hr under ice-cooling, and further at room temperature overnight. The reaction mixture was neutralized with 1N aqueous hydrochloric acid and extracted with ethyl acetate. The extract was washed successively with aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (0:10→1:1) was concentrated under reduced pressure, and a fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue was dissolved in 2N hydrochloric acid-ethyl acetate solution, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated to give the object product (186 mg).

1. temperaturecooling
2. stirringthe mixture was stirred for 6 hr under ice-
3. temperaturecooling
4. customfurther at room temperature
5. customovernight
6. extractionextracted with ethyl acetate
7. washThe extract was washed successively with aqueous sodium bicarbonate and saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure
10. washa fraction eluted with ethyl acetate-hexane (0:10→1:1)
11. concentrationwas concentrated under reduced pressure
12. washa fraction eluted with ethyl acetate
13. concentrationwas concentrated under reduced pressure
14. dissolutionThe residue was dissolved in 2N hydrochloric acid-ethyl acetate solution
15. stirringthe mixture was stirred at room temperature for 1 hr
16. concentrationThe reaction mixture was concentrated