反应详情

To a solution of 1-(pyridin-4-yl)piperidine-4-carboxylic acid ethyl ester (Tetrahedron, vol. 44, No. 23, p. 7095 (1988)) (13.4 g) in tetrahydrofuran (300 ml) was dropwise added a 2M-lithium diisopropylamide-tetrahydrofuran solution (31 ml) at −70° C. under an argon atmosphere, and the mixture was stirred at the same temperature for 45 min. To this solution was dropwise added a solution of 7-chloromethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid tert-butyl ester (7.4 g) in tetrahydrofuran (80 ml) at the same temperature, and the mixture was allowed to warm to room temperature in 5.5 hours in stirring. After completion of the reaction, aqueous ammonium chloride solution (50 ml) and water (50 ml) were added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated and the obtained residue was dissolved in methanol (150 ml). Thereto was dropwise added 1N aqueous sodium hydroxide solution (50 ml) with ice-cooling, and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated and the obtained residue was extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (chloroform:methanol=20:1-10:1) and dried under reduced pressure to give the title compound (10.87 g).

1. stirringin stirring
2. additionwere added
3. extractionthe mixture was extracted with ethyl acetate
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. customthe solvent was evaporated
6. dissolutionthe obtained residue was dissolved in methanol (150 ml)
7. temperaturecooling
8. stirringthe mixture was stirred at room temperature for 1 hour
9. customThe solvent was evaporated
10. extractionthe obtained residue was extracted with ethyl acetate
11. dry with materialdried over anhydrous sodium sulfate
12. customThe solvent was evaporated
13. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol=20:1-10:1)
14. customdried under reduced pressure